ALBERT

Description: ABSTRACT Environmental particles are believed to provoke airway inflammation in susceptible individuals by stimulating epithelial cells to release mediators that exacerbate lung diseases. Here, we sought to identify genes expressed throughout the genome by epithelial cells stimulated with TiO 2 particles. A human bronchial epithelial cell line, BEAS-2B, was stimulated with or without 40 µg TiO 2 for 2 h. RNA was purified from cells and subjected to microarray analysis. Genes exhibiting more than a twofold change in RNA expression were selected. Candidate genes were then analyzed using bioinformatics tools, including pathway, ontology, and network analyses. ITGAV mRNA expression levels were measured in BEAS-2B cells using real-time polymerase chain reaction. Among 37,803 genes, 92 genes displayed more than a twofold change in mRNA levels according to the microarray analysis; 87 genes were upregulated while five genes were downregulated. The 92 genes were classified based on functional annotation using a protein information resource database search for biological processes and a pathway search using the KEGG pathway database. These genes are related to macromolecule biosynthesis, metabolic processes and, in particular, RNA metabolism. When genes with more than a threefold change were analyzed, KIF11, ITGAV, SEMA3C, IBTK, and DEK were selected as candidate genes induced by TiO 2 -stimulated BEAS-2B cells. To validate these results, BEAS-2B cells stimulated with 40 µg TiO 2 expressed threefold higher ITGAV mRNA levels compared to those without TiO 2 particle stimulation. We conclude that KIF11, ITGAV, SEMA3C, IBTK, and DEK are candidate genes expressed by epithelial cells when stimulated with TiO 2 particles. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4-methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C-2 substitution with α-, β-, or γ-pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure–genotoxicity relationships and bioassay-guided quinoline synthesis. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT In the past few decades, there has been much concern about the adverse health effects of environmental contaminants in general and Crude Oil in particular around the Niger Delta region of Nigeria where all the crude Oil exploration is taking place. Studies have shown the repro-toxic effects of Bonny-light crude oil (BLCO). However, the insight into the mechanisms of gonadal toxicity induced by BLCO is not well known. In this study, we sought to elucidate the mechanism(s) underpinning the gonadal effects within hours of exposure to BLCO. Experimental rats were divided into five groups of four each. Animals were orally administered with a single dose of BLCO (800 mg/kg body weight) and killed at 0, 6, 12, 24, and 72 h post-treatment. The levels and time-course of induction of stress response proteins and apoptosis-related proteins like cytochorome C, caspase 3 and procaspase 9, Fas–FasL, NF-kB and TNF-α were determined to assess sequential induction of apoptosis in the rat testis. DNA damage was assessed by TUNEL assay. Administration of BLCO resulted in a significant increase in the levels of stress response proteins and apoptotis- related proteins as early as 6 h following exposure. Time-dependent elevations in the levels of the proteins were observed. The DNA damage was measured and showed time-dependent increase in the TUNEL positive cells of testicular cells. The study demonstrates induction of testicular apoptosis in adult rats following exposure to a single dose of BLCO. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Divalent lead (Pb 2+ ) is a common industrial pollutant epidemiologically associated with gastric cancers. Pb 2+ was found to promote tumorigenesis, which may include interleukin (IL)-8, a pro-inflammatory chemokine that promotes angiogenesis and tumor metastasis. Given that the gastrointestinal tract is a major route of Pb 2+ exposure, we investigated the ability of Pb 2+ to induce IL-8 expression in gastric carcinoma cells and its underlying mechanism. At a concentration of 0.1 μM, Pb 2+ induced IL-8 gene activation in gastric carcinoma AGS cells. Using a IL-8 promoter-deletion analysis, transcription factor activator protein 1 (AP-1) was identified as a necessary component of Pb 2+ -induced IL-8 gene activation. Upregulation of the IL-8 gene was abrogated by the MEK inhibitor, PD98059, and partially suppressed by the epidermal growth factor receptor inhibitors, AG1478 and PD153035. Furthermore, c-Jun protein expression was induced in cells treated with Pb 2+ , and overexpression of c-Jun enhanced Pb 2+ -induced IL-8 activation. Collectively, our findings highlight the pivotal roles of AP-1 and extracellular signal-regulated kinase in signal transduction of Pb 2+ -induced IL-8 gene activation. These molecules may be potential therapeutic targets for Pb 2+ -related inflammation leading to stomach carcinogenesis. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT In this study, we have evaluated the pulmonary toxicity of MgO nanoparticles (MgO NPs) in rats following their exposure. NPs in phosphate buffered saline + 1% Tween 80 were exposed via intratracheal instillation at a doses of 1 mg/kg or 5 mg/kg into rat lungs and evaluated for various tissue damage markers like alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid and histopathology of lungs at 1, 7, and 30 days of post-exposure intervals. A dose-dependant increase in ALP and LDH activity was observed in BAL fluids of rat lungs than sham control at all post-exposure periods ( P 〈0.05), and a dose-dependant infiltration of interstitial lymphocytes, peribronchiolar lymphocytic infiltration, and dilated and/or congested vessels at 1 day post-exposure period, worsened at 1 week period, and were reduced at 1 month at histology, indicating the pulmonary toxicity of MgO NPs. In conclusion, MgO NPs exposure produced a dose-dependent pulmonary toxicity in rats and was comparable with that of Quartz particles. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: To investigate the effects of ellagic acid on the growth inhibition of TSGH8301 human bladder cancer cells in vitro , cells were incubated with various doses of ellagic acid for different time periods. The phase-contrast microscope was used for examining and photographing the morphological changes in TSGH8301 cells. Flow cytometric assay was used to measure the percentage of viable cells, cell cycle distribution, apoptotic cells, ROS, mitochondrial membrane potential (Δ Ψm ), Ca 2+ , caspase-9 and -3 activities in TSGH8301 cells after exposure to ellagic acid. Western blotting was used to examine the changes of cell cycle and apoptosis associated proteins levels. Results indicated that ellagic acid induced morphological changes, decreased the percentage of viable cells through the induction of G0/G1 phase arrest and apoptosis, and also showed that ellagic acid promoted ROS and Ca 2+ productions and decreased the level of Δ Ψm and promoted activities of caspase-9 and -3. The induction of apoptosis also confirmed by annexin V staining, comet assay, DAPI staining and DNA gel electrophoresis showed that ellagic acid induced apoptosis and DNA damage in TSGH8301 cells. Western blotting assay showed that ellagic acid promoted p21, p53 and decreased CDC2 and WEE1 for leading to G0/G1 phase arrest and promoting BAD expression, AIF and Endo G, cytochrome c , caspase-9 and -3 for leading to apoptosis in TSGH8301 cells. On the basis of these observations, we suggest that ellagic acid induced cytotoxic effects for causing a decrease in the percentage of viable cells via G0/G1 phase arrest and induction of apoptosis in TSGH8301 cells. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Chemotherapy remains an important approach in the fight against malaria. Artemether–lumefantrine combination is widely in use due to its effectiveness against Plasmodium falciparum . Misuse in the form of multiple repeated doses of this anti-malaria drug is rampant in Nigeria. This study was designed to assess the hepatotoxic and clastogenic potential of extreme misuse of artemether–lumefantrine in rats. Graded doses of artemether–lumefantrine (1–5 mg/kg body weight) were administered by oral gavage for 6 weeks, twice daily, for 3 consecutive days per week. Artemether–lumefantrine, at all doses, did not have significant effects on the body and relative liver weight of treated group compared to the negative control group. The mean γ-glutamyltransferase, alanine, and aspartate aminotransaminase activity in groups of artemether–lumefantrine treated rats were significantly higher ( p 〈 0.05) than that of the negative control group indicating that repeated administration of artemether–lumefantrine may be hepatotoxic. Findings from histological analyses of liver cross-section support the enzyme pattern of hepatoxicity. In addition, the drug, at all experimental doses, significantly induced ( p 〈 0.05) formation of micronucleated polychromatic erythrocytes in the bone marrow cells of the treated rats compared with the negative control indicating clastogenic potential of the drug when misused. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Tattoo belongs to the group of carbamate fungicides and contains Mancozeb (ethylene(bis)dithiocarbamate) as its main constituent. The toxicity of Mancozeb to living organisms, particularly fish, is not resolved. This work investigated the effects of 96 h of exposure to 3, 5, or 10 mg L −1 of Tattoo (corresponding to 0.9, 1.5, or 3 mg L −1 of Mancozeb) on the levels of oxidative stress markers and the antioxidant enzyme system of brain, liver, and kidney of goldfish, Carassius auratus ). In liver, Tattoo exposure resulted in increased activities of superoxide dismutase (SOD) by 70%–79%, catalase by 23%–52% and glutathione peroxidase (GPx) by 49%. The content of protein carbonyls (CP) in liver was also enhanced by 92%–125% indicating extensive damage to proteins. Similar increases in CP levels (by 98%–111%) accompanied by reduced glucose-6-phosphate dehydrogenase activity (by 13%–15%) was observed in kidney of fish exposed to Tattoo; however, SOD activity increased by 37% in this tissue after treatment with 10 mg L −1 Tattoo. In brain, a rise in lipid peroxide level (by 29%) took place after exposure to 10 mg L −1 Tattoo and was accompanied by elevation of high-molecular mass thiols (by 14%). Tattoo exposure also resulted in a concentration-dependent decrease in glutathione reductase activity (by 26%–37%) in brain. The data collectively show that exposure of goldfish to 3–10 mg L −1 of the carbamate fungicide Tattoo resulted in the development of mild oxidative stress and activation of antioxidant defense systems in goldfish tissues. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Ecotoxicological studies that focus on a single endpoint might not accurately and completely represent the true ecological effects of a contaminant. Exposure to atrazine, a widely used herbicide, disrupts endocrine function and sexual development in amphibians, but studies involving live-bearing reptiles are lacking. This study tracks several effects of atrazine ingestion from female Northern Watersnakes ( Nerodia sipedon ) to their offspring exposed in utero . Twenty-five gravid N. sipedon were fed fish dosed with one of the four levels of atrazine (0, 2, 20, or 200 ppb) twice weekly for the entirety of their gestation period. Endpoints for the mothers included blood estradiol levels measured weekly and survival more than 3 months. Endpoints for the offspring included morphometrics, clutch sex ratio, stillbirth, and asymmetry of dorsal scales and jaw length. Through these multiple endpoints, we show that atrazine ingestion can disrupt estradiol production in mothers, increase the likelihood of mortality from infection, alter clutch sex ratio, cause a higher proportion of stillborn offspring, and affect scale symmetry. We emphasize the need for additional research involving other reptile species using multiple endpoints to determine the full range of impacts of contaminant exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Microcystin-LR (MC-LR) is a potent inhibitor of protein phosphatases 1 and 2A, and has potent hepatotoxicity and tumor promotion activity. Numerous studies on MC-LR toxicity have been conducted in rat hepatocytes, but few studies of the effects of microcystins on human hepatocytes have been done. In this study, HL7702 cells (a human normal liver cell line) were incubated in MC-LR for 24 h. The existence of MC-LR in HL7702 cells was confirmed. Furthermore, PP2A activity and the alteration of PP2A subunits were assessed. The results show that PP2A activity decreased from the concentration of 1 μM MC-LR, showing a concentration-dependent decline, to about 34% at 10 μM MC-LR. This activity undergone opposite change with alternations of phosphorylated Y307-PP2A/C and PP2A/C subunit but showed same change with the alteration of the ratio of methylated L309-PP2A/C to PP2A/C. B55α, a regulatory subunit of PP2A, was slightly increases in cells treated with the highest concentration of MC-LR (10 μM), and colocalized increasedly with rearranged-microtubules after 1 μM MC-LR exposure. However, the proportion of early apoptotic cells did not show any change at various concentration of MC-LR for 24 h. To our knowledge, this is the first report showing MC-LR-induced alteration of PP2A phosphatase in human cultured hepatocytes, and the mechanism of action seems to be similar as described before in vitro . The alteration of PP2A and microtubule seems to be the early event induced by MC-LR exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Nonpersistent pesticides are considered less harmful for the environment, but their impact as endocrine disruptors has not been fully explored. The pesticide Switch was applied to grape vines, and the maximum residue concentration of its active ingredients was quantified. The transactivation potential of the pesticides Acorit, Frupica, Steward, Reldan, Switch, Cantus, Teldor, and Scala and their active compounds (hexythiazox, mepanipyrim, indoxacarb, chlorpyrifos-methyl, cyprodinil, fludioxonil, boscalid, fenhexamid, and pyrimethanil) were tested on human estrogen receptor α (ERα), androgen receptor (AR) and arylhydrocarbon receptor (AhR) in vitro . Relative binding affinities of the pure pesticide constituents for AR and their effect on human breast cancer and prostate cancer cell lines were evaluated. Residue concentrations of Switch's ingredients were below maximum residue limits. Fludioxonil and fenhexamid were ERα agonists (EC 50 -values of 3.7 and 9.0 μM, respectively) and had time-dependent effects on endogenous ERα-target gene expression (cyclin D1, progesterone receptor, and nuclear respiratory factor 1) in MCF-7 human breast cancer cells. Fludioxonil, mepanipyrim, cyprodinil, pyrimethanil, and chlorpyrifos-methyl were AhR-agonists (EC 50 s of 0.42, 0.77, 1.4, 4.6, and 5.1 μM, respectively). Weak AR binding was shown for chlorpyrifos-methyl, cyprodinil, fenhexamid, and fludioxonil. Assuming a total uptake which does not take metabolism and clearance rates into account, our in vitro evidence suggests that pesticides could activate pathways affecting hormonal balance, even within permitted limits, thus potentially acting as endocrine disruptors. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Silver nanoparticles, chemically neutral particles in the size range of 1–100 nm, express strong antimicrobial activity and therefore have a broad range of applications. The increased use of consumer products with nanosilver (nanoAg) may result in its release into the environment, and may particularly affect aquatic systems. The mechanisms of the harmful effects of nanoAg against aquatic organisms are unclear. Therefore, in the present study we investigate the pro-oxidative potential of these nanoparticles in experimentally exposed crayfish Orconectes limosus . Markers of oxidative stress and parameters of the antioxidant cell defense system such as total glutathione, glutathione reductase and the level of sulfhydryl groups were examined in the hepatopancreas of both sexes of O. limosus collected seasonally from Białe Lake (Poland) and subsequently exposed to nanoAg particles for 2 weeks. Exposure to nanoAg led to a high concentration-dependent increase in the rate of lipid peroxidation and a decrease of protein-bound SH groups which indicates protein oxidation. These markers of oxidative stress were accompanied by decreased levels of thiols and reduced activity of glutathione reductase. These results indicate a deficiency of reduced glutathione and suggest that the exposed organisms have less efficient antioxidative mechanisms available to counter ROS-mediated cellular stress. Furthermore, we find that confocal microscopy is of limited utility in monitoring the presence of silver nanoparticles in tissues of exposed crayfish. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: The objective of this research was to investigate the neurotoxic effects of pyrethroid pesticide lambda-cyhalothrin by the modulation of cytochrome P450 with piperonyl butoxide in the brain of juvenile Oreochromis niloticus . The fish were exposed to 0.48 μg L −1 (1/6 of the 96-h LC 50 ) lambda-cyhalothrin and 10 μg L −1 piperonyl butoxide for 96 h and 15 days. tGSH, GSSG, TBARS contents, GPx, GR, GST, and AChE enzymes activities were determined by spectrophotometrical methods and Hsp70 content was analyzed by ELISA technique. Lambda-cyhalothrin had no significant effect on the components of GSH redox system, lipid peroxidation and Hsp70 levels but inhibited AChE activity. In the presence of piperonyl butoxide, lambda-cyhalothrin caused increases in tGSH, GSSG, TBARS and Hsp70 contents, GST activity, and decrease in AChE activity. Present results showed that in the presence of piperonyl butoxide, lambda-cyhalothrin caused neurotoxic effects by increasing oxidative stress. Adaptation to its oxidative stress effects may be supplied by GSH-related antioxidant system. Piperonyl butoxide revealed neurotoxic effect of lambda-cyhalothrin. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Environmental pollution with synthetic estrogens may pose a serious threat to reproduction of aquatic wildlife species. The current study describes the effects of 17α-ethynylestradiol (EE 2 ) on the structure of the testis in tench ( Tinca tinca ). Adult male tench were exposed to sublethal doses of EE 2 (50, 100, and 500 μg/Kg t.w.) under semistatic conditions for a period of 30 days. The condition factor (CF), testicular somatic index (TSI), and histology (including a morphometric analysis) of the testis were examined. No consistent differences were observed in the CF of EE 2 -exposed tench when compared with nonexposed fish. A significant decrease in TSI could only be observed at a 50 μg/Kg t.w. EE 2 dose (p 〈 0.05) when compared with the control group. The histopathology of the testis was associated with loss of normal tubular structure with increased doses of exposure, decrease of tubule number, degeneration in Sertoli and Leydig cells, increase in necrotic testicular cells including formation of syncytia structures and, finally, a high incidence of fish with early primary oocytes at 100 and 500 μg/Kg t.w. EE 2 . These results indicate that long-term exposure to EE 2 may produce clear negative effects on testicular structure in tench. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. Exposure to some kinds of volatile organic compounds (VOCs) leads to lung inflammation, oxidative stress, and immune modulation. However, it is suspected that sub-chronic exposure to low-dose VOCs mixture induces or aggravates lung inflammation. To clarify the effect of this exposure on lung inflammatory responses, 40 male Kunming mice were exposed in four similar static chambers, 0 (control) and three different doses of VOCs mixture (groups 1–3). The concentrations of VOCs mixture were as follows: formaldehyde, benzene, toluene, and xylene 0.10 + 0.11 + 0.20 + 0.20 mg/m 3 , 0.50 + 0.55 + 1.00 + 1.00 mg/m 3 , 1.00 + 1.10 + 2.00 + 2.00 mg/m 3 , respectively, which corresponded to 1, 5, and 10 times of indoor air quality standard in China. After 90 consecutive days of exposure (2 h/day), oxidative stress markers in lung, cellular infiltration and cytokines, chemokine, neurotrophin in bronchoalveolar lavage fluid (BALF), and immunoglobulin (Ig) in serum were examined. VOCs exposure could increase significantly reactive oxygen species (ROS) in lung, the levels of interleukin-8 (IL-8), IL-4, eotaxin, nerve growth factor (NGF), and various types of leukocytes in BALF, IgE concentration in serum. In contrast, GSH to GSSG ratio and interferon-gamma were significantly decreased following the VOCs exposure. These results indicate that the VOCs mixture-induced inflammatory response is at least partly caused by release of the ROS and mediators from the activated eosinophils, neutrophils, alveolar macrophages and epithelial cells. © 2013 Wiley Periodicals, Inc. Environ Toxicol 2013.

Description: Sick building syndrome (SBS) is a set of several clinically recognizable symptoms reported by occupants of a building without a clear cause. Neuropathy target esterase (NTE) is a membrane bound serine esterase and its reaction with organophosphates (OPs) can lead to OP-induced delayed neuropathy (OPIDN) and nerve axon degeneration. The aim of our study was to determine whether there was a difference in NTE activity in the peripheral blood mononuclear cells (PBMCs) of Japanese patients with SBS and healthy controls and whether PNPLA6 (alias NTE) gene polymorphisms were associated with SBS. We found that the enzymatic activity of NTE was significantly higher ( P 〈 0.0005) in SBS patients compared with controls. Moreover, population with an AA genotype of a single nucleotide polymorphism (SNP), rs480208, in intron 21 of the PNPLA6 gene strongly reduced the activity of NTE. Fifty-eight SNP markers within the PNPLA6 gene were tested for association in a case–control study of 188 affected individuals and 401 age-matched controls. Only one SNP, rs480208, was statistically different in genotype distribution ( P = 0.005) and allele frequency ( P = 0.006) between the cases and controls (uncorrected for testing multiple SNP sites), but these were not significant by multiple corrections. The findings of the association between the enzymatic activity of NTE and SBS in Japanese show for the first time that NTE activity might be involved with SBS. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Anticholinesterase pesticides have been widely used in agricultural and domestic settings and can be detected in the environment after long-term use. Although the acute toxic effects of chlorpyrifos and carbaryl have been well described, little is known about the chronic toxicity of the pesticides mixture. To investigate their chronic neurotoxicity, Wistar rats were exposed to chlorpyrifos, carbaryl, and their mixture (MIX) for 90 consecutive days. The activities of serum cholinesterase (ChE) as well as acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in nerve tissues were determined. Furthermore, the histopathological examination was carried out. The results showed that ChE activity significantly decreased in all treated rats except the rats treated with low dose carbaryl. Treatment with middle- and high-dose chlorpyrifos and MIX in rats significantly inhibited AChE activity in the central nervous tissues, whereas treatment with carbaryl alone did not. In sciatic nerve, AChE activity was significantly inhibited by high-dose carbaryl and MIX, but not by chlorpyrifos alone. No significant NTE inhibition was observed in all treatment groups. Histopathological examination revealed that both chlorpyrifos and MIX treatment induced hippocampal damage. However, no obvious hippocampal damage was found in carbaryl-treated rats. Carbaryl and MIX, but not chlorpyrifos alone, induced pathological damage of sciatic nerve. Taken together, all of the results indicated that chlorpyrifos and carbaryl have different toxicological target tissues in nervous system and showed corresponding effects in the nervous tissues, which may reflect the different sensitivity of central and peripheral nervous tissues to different pesticides individually and in combination. © 2013 Wiley Periodicals, Inc. Environ Toxicol 2013.

Description: ABSTRACT Bombyx mori is an important economic animal for silk production. However, it is liable to be infected by organophosphorus pesticide that can contaminate its food and growing environment. It has been known that organophosphorus pesticide including phoxim exposure may damage the digestive systems, produce oxidative stress and neurotoxicity in silkworm B. mori , whereas cerium treatment has been demonstrated to relieve phoxim-induced toxicity in B. mori . However, very little is known about the molecular mechanisms of midgut injury due to phoxim exposure and B. mori protection after cerium pretreatment. The aim of this study was to evaluate the midgut damage and its molecular mechanisms, and the protective role of cerium in B. mori following exposure to phoxim. The results showed that phoxim exposure led to severe midgut damages and oxidative stress; whereas cerium relieved midgut damage and oxidative stress caused by phoxim in B. mori . Furthermore, digital gene expression suggested that phoxim exposure led to significant up-regulation of 94 genes and down-regulation of 52 genes. Of these genes, 52 genes were related with digestion and absorption, specifically, the significant alterations of esterase, lysozyme, amylase 48, and lipase expressions. Cerium pretreatment resulted in up-regulation of 116 genes, and down-regulation of 29 genes, importantly, esterase 48, lipase, lysozyme, and α-amylase were up-regulated. Treatment with Phoxim + CeCl 3 resulted in 66 genes up-regulation and 39 genes down-regulation; specifically, levels of esterase 48 , lipase , lysozyme , and α- amylase expression in the midgut of silkworms were significantly increased. Therefore, esterase 48 , lipase , lysozyme , and α- amylase may be potential biomarkers of midgut toxicity caused by phoxim exposure. These findings may expand the application of rare earths in sericulture. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Epidemiological studies have shown that pollution derived from industrial and vehicular transportation induces adverse health effects causing broad ambient respiratory diseases. Therefore, air pollution should be taken into account when microbial diseases are evaluated. Environmental mycobacteria (EM) are opportunist pathogens that can affect a variety of immune compromised patients, which impacts significantly on human morbidity and mortality. The aim of this study was to evaluate the effect of residual oil fly ash (ROFA) pre-exposure on the pulmonary response after challenge with opportunistic mycobacteria by means of an acute short-term in vivo experimental animal model. We exposed BALB/c mice to ROFA and observed a significant reduction on bacterial clearance at 24 h post infection. To study the basis of this impaired response four groups of animals were instilled with (a) saline solution (Control), (b) ROFA (1 mg kg −1 BW), (c) ROFA and EM-infected ( Mycobacterium phlei , 8 × 10 6 CFU), and (d) EM-infected. Animals were sacrificed 24 h postinfection and biomarkers of lung injury and proinflammatory madiators were examined in the bronchoalveolar lavage. Our results indicate that ROFA was able to produce an acute pulmonary injury characterized by an increase in bronchoalveolar polymorphonuclear (PMN) cells influx and a rise in O 2 − generation. Exposure to ROFA before M. phlei infection reduced total cell number and caused a significant decline in PMN cells recruitment ( p  〈 0.05), O 2 − generation, TNFα ( p  〈 0.001), and IL-6 ( p  〈 0.001) levels. Hence, our results suggest that, in this animal model, the acute short-term pre-exposure to ROFA reduces early lung response to EM infection. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT The chronic toxicity of 12 compounds of parabens and their chlorinated by-products was investigated using 7-day Ceriodaphnia dubia test under static renewal condition in order to generate information on how to disinfect by-products of preservatives that are discharged in aquatic systems. The mortality and inhibition of reproduction tended to increase with increasing hydrophobicity and decreased with the degree of chlorination of parabens. The EC 50 values for mortality, offspring number, and first brood production ranged between 0.30–3.1, 0.047–12, and 1.3–6.3 mg L −1 , respectively. For the number of neonates, the most sensitive endpoint, the no-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) values ranged from 0.63 to 10 mg L −1 and from 1.2 to 19 mg L −1 , respectively. Methylparaben (MP), benzylparaben (BnP), and dichlorinated BnP (Cl 2 BnP) elicited a significant decrease in offspring numbers even at their lowest concentration tested; the NOEC for these compounds was determined to be less than the lowest test concentration (1.3, 0.04, and 0.63 mg L −1 for MP, BnP, and Cl 2 BnP, respectively). Propylparaben (PP), chlorinated PP, isopropylparaben (iPP), and chlorinated iPP exhibited nonmonotonic concentration-dependent response; their NOEC and LOEC values could not be determined. The multivariate approach involving principal component analysis and hierarchical cluster analysis revealed four groups that corresponded to the toxicological profiles of parabens. Our results suggested that disinfection of parabens by chlorination could reduce aquatic toxicity of original compounds. The findings obtained in our study together with the data available on paraben concentrations in aquatic systems can be used to perform preliminary risk assessment by comparing the predicted environmental concentration (PEC) with the predicted no-effect concentration (PNEC) for the marine aquatic environment. The calculated PEC/PNEC ratios ranged from 0.0012 to 0.2, with the highest value observed in MP. This suggested that there are negligible environmental risks for aquatic organisms at current use levels. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Fish are relatively sensitive to changes in their surrounding environment, including increasing pollution. Therefore, the present study was undertaken to evaluate the impact of contamination with the pendimethalin-based herbicide; Stomp ® 50% EC (50% pendimethalin as emulsive concentrate) on adults of the monosex Nile tilapia Oreochromis niloticus L. A total of 260 fish with body weights of 90 ± 5.0 g were used in the determination of the 96-h LC 50 value and of the impacts of acute exposure to pendimethalin on physiological parameters, and oxidative stress and antioxidant biomarkers. The 96-h median lethal concentration (96-h LC 50 ) value of pendimethalin for monosex Nile tilapia was determined as 4.92 mg/L. Abnormal behavioral responses of the fish and the toxic symptoms of pendimethalin exposure are described. Acute exposure to pendimethalin induced leukocytosis, hyperglobulinemia, and hyperglycemia, but resulted in nonsignificant changes in other hemato-biochemical parameters. Moreover, pendimethalin increased lipid peroxidation (LPO) and decreased levels of reduced glutathione and antioxidant enzymes; superoxide dismutase, catalase, and glutathione reductase in both liver and gill tissues, in a time-dependent manner, with maximum alterations observed in the gills rather than the liver. We conclude that although pendimethalin is moderately toxic, it does not cause hepatorenal toxicity. However, this herbicide pollutant induces major disturbances to the antioxidant system; induction of oxidative stress and LPO is the proposed toxicodynamic pathway for such stress. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT A rapid cyanobacterial bloom of Cylindrospermopsis raciborskii (3.2 × 10 4 filaments/mL) was detected early November, 2012, in the Fancsika pond (East Hungary). The strong discoloration of water was accompanied by a substantial fish mortality (even dead cats were seen on the site), raising the possibility of some toxic metabolites in the water produced by the bloom-forming cyanobacteria ( C. raciborskii ). The potential neuronal targets of the toxic substances in the bloom sample were studied on identified neurons (RPas) in the central nervous system of Helix pomatia . The effects of the crude aqueous extracts of the Fancsika bloom sample (FBS) and the laboratory isolate of C. raciborskii from the pond (FLI) were compared with reference samples: C. raciborskii ACT 9505 (isolated in 1995 from Lake Balaton, Hungary), the cylindrospermopsin producer AQS, and the neurotoxin (anatoxin-a, homoanatoxin-a) producer Oscillatoria sp. (PCC 6506) strains. Electrophysiological tests showed that both FBS and FLI samples as well the ACT 9505 extracts modulate the acetylcholine receptors (AChRs) of the neurons, evoking ACh agonist effects, then inhibiting the ACh-evoked neuronal responses. Dose–response data suggested about the same range of toxicity of FBS and FLI samples (EC 50  = 0.397 mg/mL and 0.917 mg/mL, respectively) and ACT 9505 extracts (EC 50  = 0.734 mg/mL). The extract of the neurotoxin-producing PCC 6506 strain, however, proved to be the strongest inhibitor of the ACh responses on the same neurons (EC 50  = 0.073 mg/mL). The presented results demonstrated an anatoxin-a-like cholinergic inhibitory effects of cyanobacterial extracts (both the environmental FBS sample, and the laboratory isolate, FLI) by some (yet unidentified) toxic components in the matrix of secondary metabolites. Previous pharmacological studies of cyanobacterial samples collected in other locations (Balaton, West Hungary) resulted in similar conclusions; therefore, we cannot exclude that this chemotype of C. raciborskii which produce anatoxin-a like neuroactive substances is more widely distributed in this region. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT In previous work, our laboratory developed a Drosophila model for studying the adverse effects of fungal volatile organic compounds (VOCs) emitted by growing cultures of molds. In this report, we have extended these studies and compared the toxic effects of fungal VOCs emitted from living cultures of four molds isolated after Hurricane Katrina from a flooded home in New Orleans. Strains of Aspergillus , Mucor, Penicillium , and Trichoderma were grown with wild-type larvae and the toxic effects of volatile products on the developmental stages of Drosophila larvae were evaluated. Furthermore, heterozygous mutants of Drosophila carrying the apoptotic genes, reaper and dronc , were used to assess the role of apoptosis in fungal VOCs mediated toxicity. Third-instar larvae of Drosophila carrying these apoptotic genes were exposed to fungal VOCs emitted from growing mold cultures for 10 days. The larval strains carrying apoptopic genes survived longer than the control wild type larvae; moreover, of those that survived, heterozygous reaper and dronc strains progressed to pupae and adult phases more rapidly, suggesting that fungal VOCs may induce apoptotic changes in flies. These data lend support to the use of Drosophila as an inexpensive and genetically versatile toxicological model to investigate the mechanistic basis for some of the human illnesses/symptoms associated with exposure to mold-contaminated indoor air, especially after hurricanes. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Triethyleneglycol-dimethacrylate (TEGDMA) is a monomer and widely used in dental composite resins. TEGDMA has been found to exhibit cytotoxicity and genotoxicity on many cells. However, little is known about the potential toxicological implications of TEGDMA on murine macrophage cell line RAW264.7. In this study, TEGDMA demonstrated a cytotoxic effect to RAW264.7 cells in a concentration- and time-dependent manner ( p  〈 0.05). TEGDMA was found to induce two modes of cell death in a concentration-dependent manner ( p  〈 0.05). TEGDMA-induced cell apoptosis was demonstrated by the increase in the portion of sub-G0/G1 phase and DNA ladder formation. In addition, TEGDMA exhibited genotoxicity via a dose-related increase in the numbers of micronucleus and DNA strand breaks ( p  〈 0.05). Furthermore, the activation of caspase-3, −8, and −9 were generated by TEGDMA in a dose-dependent manner ( p  〈 0.05). These results indicated that cytotoxicity and genotoxicity induced by TEGDMA in macrophages may be via DNA damage and caspase activation. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Asian sand dust (ASD), a type of particulate matter found in Asia, migrates to East Asia. The increased airborne spread of ASD has led to concerns regarding possible adverse health effects. Our group previously reported that ASD induces lung inflammation in mice, but it is still unclear whether ASD affects lymphoid organs. In this study, we investigated the effect of ASD on splenocytes in a mouse model of ASD exposure. ICR mice were intratracheally administered a single dose of normal saline (control) or ASD and were subsequently sacrificed 1 or 3 days later. TNF-α production in bronchoalveolar lavage fluids was higher at day 1, but not at day 3, after ASD administration. The enzyme-linked immunosorbent assay results showed that ASD administration increased mitogen-induced IL-2, TNF-α, and IL-6 production in splenocytes. Additionally, cell viability assay showed enhanced splenocyte proliferation at day 3, but not at day 1, after ASD administration. The electrophoretic mobility shift assay results demonstrated that nuclear factor κB (NF-κB) was activated in splenocytes on day 3, but not on day 1. In particular, NF-κB activation was detected in CD4 + and CD11b + cells on day 3. These results suggest that ASD induces subacute inflammatory responses with NF-κB activation in the spleen, in contrast to acute inflammation in the lungs. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT We hypothesize that citreoviridin (CIT) induces DNA damage in human liver-derived HepG2 cells through an oxidative stress mechanism and that N -acetyl- l -cysteine (NAC) protects against CIT-induced DNA damage in HepG2 cells. CIT-induced DNA damage in HepG2 cells was evaluated by alkaline single-cell gel electrophoresis assay. To elucidate the genotoxicity mechanisms, the level of oxidative DNA damage was tested by immunoperoxidase staining for 8-hydroxydeoxyguanosine (8-OHdG); the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH) were examined; mitochondrial membrane potential and lysosomal membranes' permeability were detected; furthermore, protective effects of NAC on CIT-induced ROS formation and CIT-induced DNA damage were evaluated in HepG2 cells. A significant dose-dependent increment in DNA migration was observed at tested concentrations (2.50–10.00 µM) of CIT. The levels of ROS, 8-OHdG formation were increased by CIT, and significant depletion of GSH in HepG2 cells was induced by CIT. Destabilization of lysosome and mitochondria was also observed in cells treated with CIT. In addition, NAC significantly decreased CIT-induced ROS formation and CIT-induced DNA damage in HepG2 cells. The data indicate that CIT induces DNA damage in HepG2 cells, most likely through oxidative stress mechanisms; that NAC protects against DNA damage induced by CIT in HepG2 cells; and that depolarization of mitochondria and lysosomal protease leakage may play a role in CIT-induced DNA damage in HepG2 cells. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Exposure to different ambient pollutants maybe more toxic to lung than exposure to a single pollutant. In this study, we discussed the inflammation and oxidative stress responses of rat lung caused by ozone and PM 2.5 versus that of rats exposed to saline, ozone, or single PM 2.5 . Wistar rats inhaled 0.8 ppm ozone or air for 4 h and then placed in air for 3 h following intratracheal instillation with 0, 0.2 (low dose), 0.8 (medium dose), 3.2 (high dose) mg/rat PM 2.5 dissolved in sterile saline (0.25 mL/rat), repeated twice per week for 3 weeks, the cumulative doses of PM 2.5 in animals were 1.2, 4.8, and 19.2 mg. Rats were sacrificed 24 h after the last (sixth) exposure. The collected bronchoalveolar lavage fluid (BALF) was analyzed for inflammatory cells and cytokines. Lung tissues were processed for light microscopic and transmission electron microscopic (TEM) examinations. Results showed that total cell number in BALF of PM 2.5 -exposed groups were higher than control ( p  〈 0.05). PM 2.5 instillation caused dose-trend increase in tumor necrosis factor alpha (TNF-α), interleukin-6, lactate dehydrogenase, and total protein of BALF. Exposure to ozone alone only caused TNF-α significant change in above-mentioned indicators of lung injury. On the other hand, ozone could enhance PM 2.5 -induced inflammatory changes and pathological characters in rat lungs. SOD and GSH-Px activities in lung were reduced in PM 2.5 -exposed rats with and without prior ozone exposure compared to control. To determine whether the PM 2.5 and ozone affect endothelium system, iNOS, eNOS, and ICAM-1 mRNA levels in lung were analyzed by real-time PCR. These data demonstrated that inflammation and oxidative stress were involved in toxicology mechanisms of PM 2.5 in rat lung and ozone potentiated these effects induced by PM 2.5 . These results have implications for understanding the pulmonary effects induced by ozone and PM 2.5 . © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT β-Naphtoflavone (β-NF) is a flavonoid and enhances oxidative stress in vertebrates with little information from aquatic invertebrates as yet. In this study, we investigated the effects of β-NF on the antioxidant defense systems of the intertidal copepod Tigriopus japonicus . To measure the β-NF-triggered changes in oxidative stress markers, such as intracellular reactive oxygen species (ROS), glutathione (GSH) concentration, residual glutathione S -transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and superoxide dismutase (SOD) activity, T. japonicus were exposed to β-NF (0.5 and 1 mg/L) for 72 h. Significant ( P  〈 0.05) induction of the intracellular ROS content (%) was observed in 1 mg/L of β-NF exposed T. japonicus , compared to the negative control and H 2 O 2 -exposed group. The GSH levels were significantly increased in the 0.5 mg/L of β-NF-exposed group for 12 h and 1 mg/L of β-NF-exposed groups for 12–24 h. GPx, GST, and GR activities showed a significant increase in the 1 mg/L β-NF-exposed group, indicating that β-NF induces oxidative stress in T. japonicus . To understand the effects of β-NF at the level of transcript expression, a 6K microarray analysis was employed. Transcript profiles of selected antioxidant-related genes were modulated after 72 h exposure to 1 mg/L of β-NF. From microarray data, 10 GST isoforms, GR, GPx, PH-GPx , and Se-GPx were chosen for a time-course test by real-time RT-PCR. T. japonicus GST-S , GST-O, GST-M , and GST-D1 were significantly increased in a 1 mg/L β-NF-exposed group. T. japonicus GPx , GR , and Se-GPx mRNA levels were also significantly increased at both concentrations. Our results revealed that oxidative stress was induced by β-NF exposure in T. japonicus . © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT This study was conducted to investigate the potential effects of diallyl disulfide (DADS) on carbon tetrachloride (CCl 4 )-induced acute hepatotoxicity and to determine the molecular mechanisms of protection offered by DADS in rats. DADS was administered orally at 50 and 100 mg/kg/day once daily for 5 consecutive days prior to CCl 4 administration. The single oral dose of CCl 4 (2 mL/kg) caused a significant elevation in serum aspartate and alanine aminotransferase activities, which decreased upon pretreatment with DADS. Histopathological examinations showed extensive liver injury, characterized by extensive hepatocellular degeneration/necrosis, fatty changes, inflammatory cell infiltration, and congestion, which were reversed following pretreatment with DADS. The effects of DADS on cytochrome P450 2E1 (CYP2E1), the major isozyme involved in CCl 4 bioactivation, were also investigated. DADS pretreatment resulted in a significant decrease in CYP2E1 protein levels in dose-dependent manner. In addition, CCl 4 caused a decrease in protein level of cytoplasmic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2 concurrent with downregulation of detoxifying phase II enzymes and a decrease in antioxidant enzyme activities. In contrast, DADS prevented the depletion of cytoplasmic Nrf2 and enhanced nuclear translocation of Nrf2, which, in turn, upregulated antioxidant and/or phase II enzymes. These results indicate that the protective effects of DADS against CCl 4 -induced hepatotoxicity possibly involve mechanisms related to its ability to induce antioxidant or detoxifying enzymes by activating Nrf2 and block metabolic activation of CCl 4 by suppressing CYP2E1. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Lead toxicity has become a serious public health concern all over the world. Previous studies have shown that lead induces biochemical and structural changes in liver. However, although lead is known to alter liver functions, the underlying molecular mechanisms of hepatotoxicity are not yet clear. We hypothesized that a correlation exists between oxidative stress, apoptosis and mitogen-activated protein kinases (MAPKs) in lead-exposed liver. Wistar rats were treated with 0, 0.5%, and 1% lead acetate for 3d, 14d, and 35d and sacrificed the next day. On 4d, oxidative stress and apoptosis were correlated with downregulated expressions of ERK1/2 and p38-MAPKα/β, and upregulated expressions of JNK1/3 in males. In females, the correlation was with downregulated expressions of ERK1/2 and upregulated expressions of p38-MAPKα/β and JNK1/3. On 15d, the correlation was observed with upregulated expressions of p38-MAPKα/β in males and downregulated expressions of p38-MAPKα/β in females. In both sexes, a correlation was observed with upregulated expressions of ERK1/2 and JNK1/3 in 1% groups. On 36d, the correlation was observed with downregulated expressions of p38-MAPKα/β in males and their upregulated expressions in females. Time-dependent increase in lipid peroxidation on 15d and 36d correlated with upregulated expressions of p38-MAPKα/β in females and ERK1/2 in 1% groups in both sexes. The lower dose induced more apoptosis up to 15d in females and the higher dose induced in males on 36d. Generally, the female livers had more p38-MAPKα/β than the male livers. On 36d, the female livers showed more p38-MAPKα/β and JNK1/3 than the male livers. In conclusion, although not clearly defined, a correlation exists among oxidative stress, apoptosis, and the MAPKs in lead-exposed hepatocytes. The sex-dependent effects may be due to differences in hormonal or other physiological mechanisms. In lead-exposed hepatocytes, the apoptosis may be induced via oxidative stress-mediated alterations in the MAPKs. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Although thallium is detrimental to all living organisms, information regarding the mutagenic and genotoxic effects of this element and its compounds remains scarce. Therefore, we tested the genotoxic and cytotoxic effects of thallium(I) acetate on human peripheral blood cells in vitro using structural chromosomal aberrations (SCAs), sister chromatid exchanges (SCEs), and single-cell gel electrophoresis (at pH 〉13 or 12.1) analysis. Whole blood samples were incubated with 0.5, 1, 5, 10, 50, or 100 µg/mL thallium salt. Exposure to this metal compound resulted in a clear dose-dependent reduction in the mitotic and replicative indices. An increase in SCAs was evident in the treated group compared with the control group, and significant differences were observed in the percentage of cells with SCAs when metaphase cells were treated with 0.5–10 µg/mL of thallium(I). The SCE test did not reveal any significant differences. We observed that a 1-h treatment with thallium(I) at pH 〉 13 significantly increased the comet length for all the concentrations tested; however, at pH 12.1, only the two highest concentrations affected the comet length. These results suggested that thallium(I) acetate induces cytotoxic, cytostatic, and clastogenic effects, as well as DNA damage. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT The objective of this study was to assess the risk of genotoxicity of d -phenothrin by measuring the oxidative stress it causes in rat liver and kidney. The level of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG)/10 6 2′-deoxyguanosine (dG) was measured by using high performance liquid chromatography (HPLC) with a diode array (DAD) and an electrochemical detector (ECD). Sixty male Wistar albino rats were randomly divided into five experimental groups and one control group of 10 rats/group. d -phenothrin was administered intraperitoneally (IP) to the five experimental groups at 25 mg/kg (Group I), 50 mg/kg (Group II), 66.7 mg/kg (Group III), 100 mg/kg (Group IV), and 200 mg/kg (Group V) for 14 consecutive days, and the control group received only the vehicle, dimethyl sulfoxide (DMSO). DNA from samples frozen in liquid nitrogen was isolated with a DNA isolation kit. Following digestion with nuclease P1 and alkaline phosphatase (ALP), hydrolyzed DNA was subjected to HPLC. The dG and 8-oxodG levels were analyzed with a DAD and ECD, respectively. In the experimental groups, the mean 8-oxodG/10 6 dG levels were 48.15 ± 7.43, 68.92 ± 20.66, 82.07 ± 14.15, 85.08 ± 28.50, and 89.14 ± 21.73 in livers and 39.06 ± 7.63, 59.69 ± 14.22, 61.13 ± 17.46, 65.13 ± 23.40, and 72.66 ± 19.04 in kidneys of Groups I, II, III, IV, and V, respectively. The mean 8-oxodG/10 6 dG levels in the control groups were 44.96 ± 12.66 for the liver and 39.07 ± 4.80 for the kidney. A statistically significant ( p  〈 0.05), dose-dependent increase in oxidative DNA damage was observed in both organs of animals exposed to d -phenothrin when compared to controls. Furthermore, the liver showed a significantly higher level of oxidative DNA damage than the kidney ( p  〈 0.01). In conclusion, d -phenothrin administered to rats intraperitoneally for 14 consecutive days generated free radical species in a dose-dependent manner and caused oxidative DNA damage in the liver and kidney. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT The increased development and use of nanoparticles in various fields may lead to increased exposure, directly affecting human health. Our current knowledge of the health effects of metal nanoparticles such as cobalt and titanium dioxide (Nano-Co and Nano-TiO 2 ) is limited but suggests that some metal nanoparticles may cause genotoxic effects including cell cycle arrest, DNA damage, and apoptosis. The growth arrest and DNA damage-inducible 45α protein (Gadd45α) has been characterized as one of the key players in the cellular responses to a variety of DNA damaging agents. The aim of this study was to investigate the alteration of Gadd45α expression in mouse embryo fibroblasts (PW) exposed to metal nanoparticles and the possible mechanisms. Non-toxic doses of Nano-Co and Nano-TiO 2 were selected to treat cells. Our results showed that Nano-Co caused a dose- and time-dependent increase in Gadd45α expression, but Nano-TiO 2 did not. To investigate the potential pathways involved in Nano-Co-induced Gadd45α up-regulation, we measured the expression of hypoxia inducible factor 1α (HIF-1α) in PW cells exposed to Nano-Co and Nano-TiO 2 . Our results showed that exposure to Nano-Co caused HIF-1α accumulation in the nucleus. In addition, hypoxia inducible factor 1α knock-out cells [HIF-1α (−/−)] and its wild-type cells [HIF-1α (+/+)] were used. Our results demonstrated that Nano-Co caused a dose- and time-dependent increase in Gadd45α expression in wild-type HIF-1α (+/+) cells, but only a slight increase in HIF-1α (−/−) cells. Pre-treatment of PW cells with heat shock protein 90 inhibitor, 17-(Allylamino)−17-demethoxygeldanamycin (17-AAG), prior to exposure to Nano-Co significantly abolished Nano-Co-induced Gadd45α expression. These results suggest that HIF-1α accumulation may be partially involved in the increased Gadd45α expression in cells exposed to Nano-Co. These findings may have important implications for understanding the potential health effects of metal nanoparticle exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Reproductive toxicities and endocrine disruptions caused by chemicals in adult males are still poorly understood. It is our objectives to understand further details of the initial adverse effects leading severe testicular toxicities of a pharmaceutical endocrine disruptor, diethylstilbestrol (DES). Downregulations of both testicular regulatory proteins, such as the steroidogenic acute regulatory protein (StAR) and the peripheral benzodiazepine receptor (PBR), which play important roles in the transport of cholesterol into the mitochondria, and cytochrome P450 mediating the cholesterol side chain cleavage reaction (P450scc), were observed in the rat orally administered DES (340 μg/kg/2 days) for 2 weeks. We found that after only 1 week treatment with DES, the blood and testicular testosterone (TS) levels were drastically decreased without abnormalities of the StAR and PBR; however, the protein and mRNA levels of P450scc were diminished. Decrease in the conversion rate of cholesterol to pregnenolone was delayed in the in vitro assay using the testicular mitochondrial fraction from the rat treated with DES for 1 week. When the precursors in TS biosynthesis containing the testis were identified and determined by liquid chromatography-mass spectrometry analysis, decreased levels of all precursors except cholesterol were observed. In conclusion, suppressed cytochrome P450scc expression in adult male rat was identified as an initial target of DES in testicular steroidogenesis disorder leading reproductive toxicities. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Increasing use of pesticides all over the world makes it necessary to reveal the toxic risk in populations of nontargeted organisms. Bendiocarb is one of the 12 insecticides recommended by the World Health Organization for use in malaria control in Africa, and is used against a variety of insects. The liver has an important role in its process of detoxication and excretion. In our experiment 56 adult rabbits of breed HY+, 28 males and 28 females were used. Animals were divided into groups (control, days 10, 20, 30 of bendiocarb administration). The presence of many binucleated hepatocytes, the highest number of liver cells and their decreased size at 10 day after bendiocarb administration was observed as an evidence of the hepatic regeneration. After the long-term treatment pronounced changes were presented such as vacuolization and dilatation of hepatocytes, dilatation of sinusoids between hepatocytes, and focal infiltration of inflammatory cells. Numerous cells with caspase-3 activity were present throughout the organ, most commonly around the portal tract and close to the central vein. Short and long-term bendiocarb treatment showed the central vein thickened rim with increased deposition of collagen, spreading of collagen fibers into the perisinusoidal, and pericellular space surrounding the central veins, and septal fibrosis extended from the portal tract. Subsequently, presence of the lipid vacuoles both in the liver parenchyma and inner of the hepatocytes were observed. These results suggest that bendiocarb treatment leads to increased cell death, liver perisinusoidal fibrosis, and steatosis, especially during the long-term administration. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Humic acid (HA) has been implicated as a contributory factor for blackfoot disease, which is an endemic peripheral vascular disease. We investigated the effect of HA on the regulation of endothelial nitric oxide (NO) synthase (eNOS) in human umbilical vein endothelial cells (HUVECs) to evaluate the involvement of eNOS and related factors in peripheral vascular impairment with HA exposure. Treatment of HUVECs with HA induced upregulation of eNOS. This result coincides with those of previous studies. Furthermore this is the first study to report that HA induces upregulation of heat shock protein (Hsp)90α, Hsp90β, eNOS phosphorylation at Ser1177, and eNOS phosphorylation at Thr495, as compared to that in the control. In contrast, treatment with BAPTA, an intracellular Ca 2+ chelator, inhibited upregulation of these proteins induced by HA. This study demonstrates that HA treatment leads to increases in both Hsp90α and Hsp90β proteins and indicates that Hsp90α leads to eNOS phosphorylation at Ser1177 and that Hsp90β leads to eNOS phosphorylation at Thr495, respectively. Upregulation of eNOS, Hsp90α, and Hsp90β in HUVECs is regulated by intracellular Ca 2+ accumulation induced by HA. These results suggest that upregulation of eNOS phosphorylation at Ser1177 and eNOS phosphorylation at Thr495 produce NO and superoxide anions, respectively, resulting in generation of peroxynitrite, which causes impairment of vascular endothelial cells. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Mortality, genotoxicity, and cytotoxicity of the 48% chlorpyrifos (CPF)-based formulations Lorsban* 48E ® and CPF Zamba ® were evaluated on Cnesterodon decemmaculatus (Jenyns, 1842) (Pisces, Poeciliidae) under laboratory conditions. Induction of micronucleus (MN) and alterations in the erythrocyte/erythroblast frequencies were employed as end points for genotoxicity and cytotoxicity, respectively. For Lorsban* 48E ® , mean values of 0.13 and 0.03 mg/L were determined for LC 50 at 24 and 96 h, respectively, and these concentrations reached mean values of 0.40 and 0.21 mg/L for CPF Zamba ® . Mortality values increased as a positive linear function of the CPF Zamba ® concentrations, but not for Lorsban* 48E ® concentrations. There was no significant relationship between mortality and exposure time within the 0–96 h period for both formulations. LC 50 values indicated that the fish were seven fold more sensitive to Lorsban* 48E ® than to CPF Zamba ® . Lorsban* 48E ® within the concentration range of 0.008–0.025 mg/L increased MN frequency at both 48 and 96 h of treatment. Similar results were also observed when fish were exposed to 0.052–0.155 mg/L of CPF Zamba ® , regardless of the exposure time. Cellular cytotoxicity was found after Lorsban* 48E ® and CPF Zamba ® treatments for all concentrations and time exposures, estimated by a decrease in the frequency of mature erythrocytes and a concomitant enhanced frequency of erythroblasts in circulating blood. Furthermore, our results demonstrated that Lorsban* 48E ® and CPF Zamba ® should be considered as CPF-based commercial formulations with marked genotoxic and cytotoxic properties. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Greater exposure to Pb(II) increases the likelihood of harmful effects in the environment. In this study, the aquatic unicellular alga Chlorella protothecoides ( C. protothecoides ) and Chlorella vulgaris ( C. vulgaris ) were chosen to assess the acute and chronic toxicity of Pb(II) exposure. Results of the observations show dose-response relationships could be clearly observed between Pb(II) concentration and percentage inhibition (PI). Exposure to Pb(II) increased malondialdehyde (MDA) content by up to 4.22 times compared with the control, suggesting that there was some oxidative damage. ANOVA analysis shows that Pb(II) decreased chlorophyll (chl) content, indicating marked concentration-dependent relationships, and the lowest levels of chl a, chl b, and total-chl were 14.53, 18.80, and 17.95% of the controls, respectively. A real-time PCR assay suggests the changes in transcript abundances of three photosynthetic-related genes. After 120 h exposure Pb(II) reduced the transcript abundance of rbc L, psa B, and psb C, and the relative abundances of the three genes of C. protothecoides and C. vulgaris in response to Pb(II) were 54.66–98.59, 51.68–95.59, 37.89–95.48, 36.04–94.94, 41.19–91.20, and 58.75–96.80% of those of the controls, respectively. As for 28 d treatments, the three genes displayed similar inhibitory trend. This research provides a basic understanding of Pb(II) toxicity to aquatic organisms. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Bisphenol A (BPA) is employed in the manufacturing of epoxy, polyester-styrene, and polycarbonate resins, which are used for the production of baby and water bottles and reusable containers, food and beverage packing, dental fillings and sealants. The study was designed to examine the effects of 8-week exposure (a full cycle of spermatogenesis) to BPA alone and in a combination with X-irradiation on the reproductive organs and germ cells of adult and pubescent male mice. Pzh:Sfis male mice were exposed to BPA (5, 10, and 20 mg/kg) or X-rays (0.05 Gy) or to a combination of both (0.05 Gy + 5 mg/kg bw BPA). The following parameters were examined: sperm count, sperm motility, sperm morphology, and DNA damage in male gametes. Both BPA and X-rays alone diminished sperm quality. BPA exposure significantly reduced sperm count in pubescent males compared to adult mice, with degenerative changes detected in seminiferous epithelium. This may suggest a higher susceptibility of germ cells of younger males to BPA action. Combined BPA with X-ray treatment enhanced the harmful effect induced by BPA alone in male germ cells of adult males, whereas low-dose irradiation showed sometimes protective or additive effects in pubescent mice.

Description: ABSTRACT It has been demonstrated that the organic damages of animals can be caused by exposure to lanthanide oxides or compounds. However, the molecular mechanism of CeCl 3 -induced kidney injury remains unclear. In this study, the mechanism of nephric damage in mice induced by an intragastric administration of CeCl 3 was investigated. The results showed that Ce 3+ was accumulated in the kidney, which in turn led to oxidative stress, severe nephric inflammation, and dysfunction in mice. Furthermore, CeCl 3 activated nucleic factor κB, which in turn increased the expression levels of tumor necrosis factor α, macrophage migration inhibitory factor, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-18, interleukin-1β, cross-reaction protein, transforming growth factor-β, interferon-γ, and CYP1A1, while suppressed heat shock protein 70 expression. These findings implied that Ce 3+ -induced kidney injury of mice might be associated with oxidative stress, alteration of inflammatory cytokine expression, and reduction of detoxification of CeCl 3 . © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Polycyclic aromatic hydrocarbons (PAHs) are the most common contaminants in the environment. The primary focus on the toxicity of PAHs is their ability to activate the aryl hydrocarbon receptor (AhR)-mediated pathway and lead to carcinogenesis in different organisms. However, the influence of PAHs on the antioxidant system in mammalian systems has received only limited attention. In the present study, we observed that the intraperitoneal injection of 100 mg/kg 3-methylcholanthrene (3MC) into mice significantly increased reactive oxygen species (ROS) levels and malondialdehyde (MDA) contents and decreased glutathione (GSH) contents and the activity of total antioxidant capacity (T-AOC), indicating that serious oxidative stress had been induced in the liver of mice. Then, the oxidative stress signal activated the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway by enhancing the mRNA levels of Nrf2, p38, and Erk2. Moreover, the mRNA levels of Nrf2/ARE target genes, including glutathione peroxidase (Gpx), glutathione reductase (GR), glutathione synthetase (GS), NAD(P)H: quinone oxidoreductase 1 (Nqo1), superoxide dismutase 1 (Sod1) , and Sod2 , increased significantly after treatment with 3MC for 24 hours. The hepatic levels of NQO1 and the activities of GR and GS were also significantly enhanced at 24 hours after 3MC treatment. Because the expression of NQO1 is co-regulated by Nrf2/ARE and AhR/XRE in mammalian tissues, NQO1 may play an important role in protecting against the oxidative stress induced by 3MC. Taken together, our findings suggested that acute exposure to 3MC altered the cellular redox balance in hepatocytes to trigger Nrf2-regulated antioxidant responses, which may represent an adaptive cell defense mechanism against the oxidative stress induced by PAHs. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Exposure to benzidine has been known to induce human cancers, particularly bladder carcinomas. In this study, the zebrafish model was used to investigate the developmental toxicity of benzidine. Embryos at 6 h postfertilization (hpf) that were exposed to benzidine exhibited embryonic death in a dose- and time-dependent manner. Benzidine induced malformations in zebrafish, such as small brain development, shorter axes, and a slight pericardial edema. High concentrations (50, 100, and 200 µM) of benzidine triggered widespread apoptosis in the brain and dorsal neurons, as evidenced by acridine orange and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays. Real-time polymerase chain reaction analysis also showed that benzidine treatment affected p53 , bax , and noxa expression. Decreases in specific brain markers, such as emx1 in the telencephalon, ngn1 in differentiated neurons, and otx2 in the midbrain, were observed in benzidine-treated embryos at 24 hpf. Conversely, no overt changes to pax2.1 expression in the midbrain–hindbrain boundary were found. Moreover, the use of Tg( HuC : GFP ) zebrafish showed that benzidine caused a malformation of the telencephalon region. Our findings show that benzidine exposure triggers widespread apoptosis in the zebrafish brain and dorsal neurons, resulting in the development of an abnormal telencephalon. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Bio-oils, which are multicomponent mixtures, were produced from two different biomass (rice straw (rice oil) and sawdust of oak tree (oak oil)) by using the slow pyrolysis process, and chemical compositional screening with GC-MS detected several hazardous compounds in both bio-oil samples. The two bio-oils vary in their chemical compositional nature and concentrations. To know the actual hazard potentialities of these bio-oils, toxicological assessments were carried out in a comparative approach by using in vitro (Jurkat T and HepG2 cell) as well as in vivo ( Caenorhabditis elegans ) systems. A dose-dependent increase in cytotoxicity, cell death (apoptosis), and genotoxicity were observed in cultured cell systems. Similarly, the in vivo system, C. elegans also displayed a dose-dependent decrease in survival. It was found that in comparison with rice oil, oak oil displayed higher toxicity to all models systems, and the susceptibility order of the model systems were Jurkat T 〉 HepG2 〉 C. elegans . Pursuing the study further toward the underlying mechanism by exploiting the C. elegans mutants screening assay, the bio-oils seem to mediate toxicity through oxidative stress and impairment of immunity. Taken together, bio-oils compositions mainly depend on the feedstock used and the pyrolysis conditions which in turn modulate their toxic potentiality. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT 2-Aminobiphenyls (2-ABP) induces oxidative DNA damage and leads to apoptosis. The precise signaling pathways of inducing apoptosis in vitro are still unknown. This study provides insight into the relationship between 2-ABP-induced apoptosis and the activation of MAPK and downstream transcription factors using pharmacological inhibitors of ERK, p38, and JNK pathways. Results showed that 2-ABP induced the activation of ERK and JNK but not p38. The ERK/JNK pathways downstream transcription factors, c-Jun and ATF-2, were also activated by 2-ABP. The inhibitory effects of ERK inhibitor, U0126, on 2-ABP-induced caspase-3 activity were not detected. However, JNK inhibitor, SP600125, significantly attenuated the caspase-3 activity induced by 2-ABP. The expression of the transcription factors c-Jun and ATF-2 were decreased in 2-ABP treated cells in the presence of ERK/JNK inhibitors, suggesting that the expression of ERK/JNK pathways leads to the downstream activation of c-Jun and ATF-2. N-acetylcysteine, an ROS scavenger, inhibited 2-ABP-induced activation of ERK and JNK, the cell death and caspase-3 activity, which suggested that oxidative stress plays a crucial role in apoptosis through activation of caspase-3 in a ROS/JNK-dependent signaling cascade. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Paraquat (PQ), which is used extensively as a potent herbicide throughout the world, is highly toxic in humans. We aimed to determine PQ-induced biochemical and histologic changes in the kidneys, and to evaluate the ability of the protective effects of caffeic acid phenethyl ester (CAPE) against PQ-induced injury in rats. Forty-eight rats were divided into eight groups of six: Group 1: Control; Group 2: 10 μmol/kg CAPE; Group 3: 15 mg/kg PQ; Group 4: 30 mg/kg PQ; Group 5: 45 mg/kg PQ; Group 6: 15 mg/kg PQ+CAPE; Group 7: 30 mg/kg PQ+CAPE; Group 8: 45 mg/kg PQ+CAPE. PQ and CAPE were injected intraperitoneally. The levels of the total oxidant status (TOS) and total antioxidant status (TAS) were determined in the supernatants of the excised left kidney. Right kidney tissue of each rat was removed to obtain a histologic score. When PQ-administrated (15, 30, 45) groups compared with other groups, TOS values were found to be significantly higher ( p  〈 0.01). PQ (15, 30, 45) groups had significantly diminished values of TAS than the other groups ( p  〈 0.001). Of histologic score evaluation, only the PQ45 group had a significantly higher value than the sham, and CAPE groups ( p  〈 0.05). Moreover, in CAPE+PQ45 group, the level of histologic score was decreased compared to PQ45 group ( p  〈 0.001). In conclusion, the evaluation of the data suggests that CAPE can be used to prevent the acute effects of PQ nephrotoxicity. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Tilapia were exposed to sublethal concentrations of 0, 0.2, 2, 20, or 200 μg/L for 30 days, and then transferred to methomyl-free water for 18 days. GST, GPx, GR, GSH, and GSSG in tilapia serum were examined at 0, 6, 12, 18, 24, and 30 days after methomyl exposure and at 18 days after transferring to methomyl-free water. There were no significant changes in antioxidants activities and contents in serum of tilapia exposed to 0.2 μg/L. Significant increases in GST, GR, GPx, and GSSG accompanied by a decrease in GSH were observed following methomyl exposure to 2, 20, or 200 μg/L, suggesting the presence of oxidative stress. Thus, it would appear the 0.2 μg/L methomyl might be considered the no observed adverse effect level. Recovery data showed that the effects produced by lower concentration of 20 μg/L were reversible but not at the higher 200 μg/L concentration. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Environmental estrogens are major cause of endocrine disruption in vertebrates, including aquatic organisms. Teleosts are valuable and popular models for studying the effects of endocrine disrupting chemicals (EDCs) in the environment. In the present study, we investigated the changes caused by exposure to the synthetic estrogens 17α-ethynylestradiol (EE 2 ) and diethylstilbesterol (DES) during early stages of growth and sex differentiation of air-breathing catfish, Clarias gariepinus , at the morphological, histological, and molecular levels. Catfish hatchlings, 0 day post hatch (dph) were exposed continuously to sublethal doses of EE 2 (50 ng/L) and DES (10 ng/L) until 50 dph and subsequently monitored for ovarian structural changes and alteration in the gene expression of steroidogenic enzymes till adulthood. Treated fish exhibited morphological deformities such as spinal curvature, stunted growth, and yolk-sac fluid retention. In addition to ovarian atrophy, DES-treated fish showed either rudimentary or malformed ovaries. Detailed histological studies revealed precocious oocyte development as well as follicular atresia. Further, transcript levels of various steroidogenic enzyme and transcription factor genes were altered in response to EE 2 and DES. Activity of the rate-limiting enzyme of estrogen biosynthesis, aromatase, in the ovary as well as the brain of treated fish was in accordance with transcript level changes. These developmental and molecular effects imparted by EE 2 and DES during early life stages of catfish could demonstrate the deleterious effects of estrogen exposure and provide reliable markers for estrogenic EDCs exposure in the environment. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Domestic exposure to biomass smoke represents the second cause of chronic obstructive lung disease. Previous studies have shown that exposure of guinea pigs to wood smoke is capable of generating oxidative stress in lung tissue, and this may involve a failure at a mitochondrial level, given its close relation with the production of reactive oxygen species (ROS). The purpose of this study was to evaluate, in guinea pigs exposed to wood smoke, the lung mitochondrial functionality through O 2 consumption measurement and the determination of the mitochondrial complexes enzymatic activity. We found that normal and maximum respiration decreased at 15 and 30 min of wood smoke exposure, recovering its normal values at 180 min. The same behavior was observed for the respiratory control rate (RCR) and the ADP/O value. Complex I activity decreased significantly after 30 min of exposure and it returned to baseline after 180 min. The greatest alteration was observed by the decrease of 85% on complex IV activity at 30 min of exposure, which returned to control values after 180 min of exposure. It is concluded that even when wood smoke exposure induces severe mitochondrial respiration alterations at the first 30 min, it seems that there is one or many ways by which mitochondria can reinstate its normal function after 180 min of exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTACT Organophosphates (OPs) pesticides are among the most toxic synthetic chemicals purposefully added in the environment. The common use of OP insecticides in public health and agriculture results in an environmental pollution and a number of acute and chronic poisoning events. Present study was aimed to evaluate the potential of monocrotophos and quinalphos to effect the redox status and glutathione (GSH) homeostasis in rat tissues and find out whether antioxidant vitamins have some protection on the pesticide-induced alterations. The results showed that these pesticides alone or in combination, caused decrease in the levels of GSH and the corresponding increase in the levels of GSSG, decreasing the GSH/GSSG ratio. The results also showed that NADPH/NADP + and NADH/NAD + ratios were decreased in the liver and brain of rats on exposure with mococrotophos, quinalphos, and their mixture. These pesticides, alone or in combination, caused alterations in the activities of GSH reductase and glucose-6-phosphate dehydrogenase in the rat tissues. However, the expression of the GSH recycling enzymes did not show significant alterations as compared to control. From the results, it can be concluded that these pesticides generate oxidative stress but their effects were not synergistic when given together and prior feeding of antioxidant vitamins tend to reduce the toxicities of these pesticides. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Exposure to lanthanoids (Ln) elicits an adverse response such as oxidative injury of lung in animals and human. The molecular targets of Ln remain unclear. In the present study, the function and signal pathway of nuclear factor erythroid 2 related factor 2 (Nrf2) in LaCl 3 -induced oxidative stress in mouse lung were investigated. Mice were exposed to 2, 5, and 10 mg/kg body weight by nasal administration for 6 consecutive months. With increased doses, La was markedly accumulated and promoted the reactive oxygen species (ROS) production in the lung, which in turn resulted in peroxidation of lipids, proteins and DNA, and severe pulmonary damages. Furthermore, LaCl 3 exposure could significantly increase levels of Nrf2, heme oxygenase 1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC) expressions in the LaCl 3 -exposed lung. These findings imply that the induction of Nrf2 expression is an adaptive intracellular response to LaCl 3 -induced oxidative stress in mouse lung, and that Nrf2 may regulate the LaCl 3 -induced pulmonary damages. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Microcystin-LR (MC-LR), a potent specific hepatotoxin produced by cyanobacteria, has recently been reported to show neurotoxicity. Our previous study demonstrated that MC-LR caused the reorganization of cytoskeleton architectures and hyperphosphorylation of the cytoskeletal-associated proteins tau and HSP27 in neuroendocrine PC12 cell line by direct PP2A inhibition and indirect p38 mitogen-activated protein kinase (MAPK) activation. It has been shown that oxidative stress is extensively associated with MC-LR toxicity, mainly resulting from an excessive production of reactive oxygen species (ROS). However, the mechanisms by which ROS mediates the cytotoxic action of MC-LR are unclear. In the present study, we investigated whether ROS might play a critical role in MC-LR-induced hyperphosphorylation of microtubule-associated protein tau and the activation of the MAPKs in PC12 cell line. The results showed that MC-LR had time- and concentration-dependent effects on ROS generation, p38-MAPK activation and tau phosphorylation. The time-course studies indicated similar biphasic changes in ROS generation and tau hyperphosphorylation, which started to increase within 1 h and reached the maximum level at 3 h followed by a decrease after prolonged treatment. Furthermore, pretreatment with the antioxidants, N -acetylcysteine and vitamin C, significantly decreased MC-LR-induced ROS generation and effectively attenuated p38-MAPK activation as well as tau hyperphosphorylation. Taken together, these findings suggest that ROS generation triggered by MC-LR is a key intracellular event that contributes to an induction of p38-MAPK activation and tau phosphorylation, and that blockade of this ROS-mediated redox-sensitive signal cascades may attenuate the toxic effects of MC-LR. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Formaldehyde, a ubiquitous environmental pollutant, has long been suspected of causing adverse male reproductive effects. However, the molecular and cellular mechanisms underlying this phenomenon remain elusive. The overall aim of this study is to clarify the role of autophagy in male reproductive injuries induced by formaldehyde exposure, by which we can further understand the molecular mechanism of spermatogenesis and develop new targets for prevention and treatment of male infertility. In this study, electron microscopy, Western blot, and RT-PCR analysis were used to detect autophagy in testicular tissues. Moreover, testicular weights, histopathology, and morphometry were used to evaluate the reproductive injuries of formaldehyde exposure. We found that formaldehyde exposure-induced autophagy in testicular tissues was dose dependent. Increasing autophagosomes in spermatogenetic cells was observed by electron microscopy in formaldehyde exposure group. In addition, RT-PCR and Western blot analysis showed the transcription levels of the LC3-II, as well as the conversion from LC3-I to LC3-II, an indicator of autophagy, significantly increased in testicular tissue of formaldehyde exposure group in a dose dependent manner when compared with those in control group. Furthermore, the alterations of autophage were basically consistent with the changes in testicular weight and morphologic findings. In summary, formaldehyde exposure triggered autophagy, and autophagy may be a scathing factor responsible for male reproductive impairment induced by formaldehyde. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: The need for powerful new tools to detect the effects of chemical pollution, in particular of persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons (PAHs) on Mediterranean cetaceans led us to develop and apply a suite of sensitive biomarkers for integument biopsies of stranded and free-ranging animals. This multi-response ex vivo method has the aim to detect toxicological effects of contaminant mixtures. In the present study, we applied an ex vivo assay using skin biopsy and liver slices, combining molecular biomarkers [Western blot of Cytochrome P450 1A1 (CYP1A1) and Cytochrome P450 2B (CYP2B)] and gene expression biomarkers (Quantitative real-time PCR of CYP1A1, heat shock protein 70, estrogen receptor alpha and E2F transcription factor) in response to chemical exposure [organochlorines compounds (OCs), polybrominated diphenyl ethers (PBDEs), and PAHs] for stranded Mediterranean Stenella coeruleoalba. The main goal of this experiment was to identify the biomarker and/or a suite of biomarkers that could best detect the presence of a specific class of pollutants (OCs, PBDEs, and PAHs) or a mixture of them. This multi-response biomarker methodology revealed an high sensitivity and selectivity of responses (such as CYP1A and ER α mRNA variations after OCs and PAHs exposure) and could represent a valid future approach for the study of inter- and intra-species sensitivities to various classes of environmental contaminants. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Metal toxicity may occur after exposure from many sources. Oxidative stress is thought to be involved in manganese-induced toxicity and leads to various health disorders. Silymarin (SIL), a natural flavonoid, has been reported to have many benefits and medicinal properties. The aim of this study was to assess the toxicity of manganese (Mn) on oxidative stress and DNA damage in the kidney of rats and its alleviation by SIL. Manganese was given orally in drinking water (20 mg MnCl 2 /mL) with or without SIL administration (100 mg /kg intraperitoneally) for 30 days. Our data showed that SIL significantly prevented Mn induced nephrotoxicity, indicated by both diagnostic indicators of kidney injury like plasma urea, uric acid and creatinine and urinary electrolyte levels and by histopathological analysis. Moreover, Mn-induced profound elevation of the production of reactive oxygen species (ROS) and altered the levels of oxidative stress related biomarkers in kidney tissue. This is evidenced by the increase of lipid peroxidation, protein carbonylation, DNA fragmentation and urinary hydrogen peroxide, while, the activities of enzymatic antioxidant and glutathione level were decreased. Treatment with SIL reduced the alterations in the renal and urine markers, decreasing lipid peroxidation markers, increasing the antioxidant cascade and decreasing the Mn-induced damage. All these changes were supported by histopathological observations. These findings suggested that the inhibition of Mn-induced damage by SIL was due at least in part to its antioxidant activity and its capacity to modulate the oxidative damage. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Pyrethroid insecticides are widely used on agricultural crops, as well as for nurseries, golf courses, urban structural and landscaping sites, residential home and garden pest control, and mosquito abatement. Evaluation of sensitive marine and estuarine species is essential for the development of toxicity testing and risk-assessment protocols. Two estuarine crustacean species, Americamysis bahia (mysids) and Palaemonetes pugio (grass shrimp), were tested with the commonly used pyrethroid compounds, lambda-cyhalothrin, permethrin, cypermethrin, deltamethrin, and phenothrin. Sensitivities of adult and larval grass shrimp and 7-day-old mysids were compared using standard 96-h LC 50 bioassay protocols. Adult and larval grass shrimp were more sensitive than the mysids to all the pyrethroids tested. Larval grass shrimp were approximately 18-fold more sensitive to lambda-cyhalothrin than the mysids. Larval grass shrimp were similar in sensitivity to adult grass shrimp for cypermethrin, deltamethrin, and phenothrin, but larvae were approximately twice as sensitive to lambda-cyhalothrin and permethrin as adult shrimp. Acute toxicity to estuarine crustaceans occurred at low nanogram per liter concentrations of some pyrethroids, illustrating the need for careful regulation of the use of pyrethroid compounds in the coastal zone. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: The aim of this study is to investigate the effects of subchronic exposure to chlorpyrifos on reproductive toxicology of male rats. Forty healthy male rats were divided into four groups: three exposure groups and a control group. Chlorpyrifos was administered orally to male rats at 0, 2.7, 5.4, and 12.8mg/kg for 90 days to evaluate the toxic alterations in testicular histology, testicular marker enzyme activities and related genes expression levels, sperm dynamics, and testosterone levels. The body weight and the testis weight of animals did not show any significant changes. Chlorpyrifos brought about marked reduction in testicular sperm counts, sperm motility, and significant growth of sperm malformation rate in exposed males. Histopathological examination of testes showed mild to severe degenerative changes in seminiferous tubules at various dose levels. The levels of testosterone (T) showed a decreasing tendency, and there was a statistical difference between the 5.4, 12.8 mg/kg groups, and the control group. The levels of follicle stimulating hormone (FSH) were significantly increased in 5.4 and 12.8 mg/kg groups, but there were no obvious effects on the levels of luteinizing hormone (LH) and estradiol (E 2 ). A significant increase in the activities of LDH and LDH-x was observed in chlorpyrifos exposed rats in 5.4 and12.8 mg/kg groups, but the expression levels of related genes had no significant differences between chlorpyrifos exposure groups and the control group. These results suggest that chlorpyrifos has adverse effects on reproductive system of male rats. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: This study evaluated the effects of β-diketone antibiotics (DKAs) on the development of embryo-larval zebrafish ( Danio rerio ). When exposure to DKAs, developmental malformations, such as hatching delay, curved body axis, pericardial edema, uninflated swim bladder and yolk sac edema, were observed at 120 h postfertilization (hpf). The estimated 120 hpf nominal concentrations of no observed effect concentration and lowest observed effect concentration for DKAs were 18.75 and 37.50 mg/L, respectively, suggesting that DKAs have much lower toxicity than other persistent pollutants. Following DKA exposure, embryonic heart rates were significantly reduced as compared to the controls at 48 and 60 hpf. The peak bending motion frequency appeared 1 h earlier than in control embryos. The 2.34 and 9.38-mg/L treatment groups had a higher basal swim rate than control groups at 120 hpf in both light and light-to-dark photoperiod experiments. The occurrence of high speed swim rates was enhanced approximately threefold to sevenfold in the 2.34 and 9.38 mg/L treatments compared to the control. Glutathione (GSH) concentrations in the 2.34 and 9.38-mg/L treatments were significantly higher than the control at 72 hpf, suggesting that GSH production was induced at the end of the hatching period. When exposed to DKAs, zebrafish superoxide dismutase enzyme (SOD) activities were significantly inhibited in the early embryonic period, demonstrating that the clearing ability in zebrafish was lower than the generation rate of free radicals. In summary, the combined DKAs were developmentally toxic to zebrafish in their early life stages and had the ability to impair individual behaviors that are of great importance in the assessment of their ecological fitness. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: The development of agricultural activities coincides with the increased use of pesticides to control pests, which can also be harmful to nontarget insects such as bees. Thus, the goal of this work was assess the toxic effects of thiamethoxam on newly emerged worker bees of Apis mellifera (africanized honeybee—AHB). Initially, we determined that the lethal concentration 50 (LC 50 ) of thiamethoxam was 4.28 ng a.i./μL of diet. To determine the lethal time 50 (LT 50 ), a survival assay was conducted using diets containing sublethal doses of thiamethoxam equal to 1/10 and 1/100 of the LC 50. The group of bees exposed to 1/10 of the LC 50 had a 41.2% reduction of lifespan. When AHB samples were analyzed by morphological technique we found the presence of condensed cells in the mushroom bodies and optical lobes in exposed honeybees. Through Xylidine Ponceau technique, we found cells which stained more intensely in groups exposed to thiamethoxam. The digestive and regenerative cells of the midgut from exposed bees also showed morphological and histochemical alterations, like cytoplasm vacuolization, increased apocrine secretion and increased cell elimination. Thus, intoxication with a sublethal doses of thiamethoxam can cause impairment in the brain and midgut of AHB and contribute to the honeybee lifespan reduction. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Microglia are the major component of intrinsic brain immune system in neuroinflammation. Although wogonin expresses anti-inflammatory function in microglia, little is known about the molecular mechanisms of the protective effect of wogonin against microglia activation. The aim of this study was to evaluate how wogonin exerts its anti-inflammatory function in BV2 microglial cells after LPS/INFγ administration. Wogonin not only inhibited LPS/ INFγ-induced PGE2 and NO production without affecting cell viability but also exhibited parallel inhibition on LPS/INFγ-induced expression of iNOS and COX-2 in the same concentration range. While LPS/INFγ-induced expression of P-p65 and P-IκB was inhibited by wogonin — only weak inhibition on P-p38 and P-JNK were observed, whereas it significantly attenuated the P-ERK1/2 and its upstream activators P-MEK1/2 and P-Src in a parallel concentration-dependent manner. These results indicated that the blockade of PGE2 and NO production by wogonin in LPS/INFγ-stimulated BV2 cells is attributed mainly to interference in the Src-MEK1/2-ERK1/2-NFκB-signaling pathway. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Significant correlations between concentrations of PBDEs and heavy metals were observed in the human body. However, there is a lack of evidence on the linkage between the uptake of heavy metals and PBDEs. This study is the first report on the BDE-47 uptake profile in a human cell line. Hg and As exposures to KERTr (human skin derived keratinocyte) did not significantly ( p 〉 0.05) affect the uptake of BDE47, whereas Pb and Cd significantly ( p 〈 0.05) affected the uptake of BDE-47 in KERTr. The change in K m was minor after exposure to all heavy metals. The maximum transport rate ( V max ) after exposure to Pb ( V max : 5.23 ± 0.49) and As ( V max : 4.95 ± 0.60) was significantly increased when compared with the background of the KERTr cell line ( V max : 4.07 ± 0.35). Real-time RT-PCR indicated that OATP-B, OATP-D, and OATP-E were expressed in the KERTr cell line. The upregulation or downregulation of OATP B and D genes were minor after exposure to heavy metals, but the OATP E gene was upregulated by three to fourfold in KERTr cell line after exposure to Pb an Cd, which may explain the significant increase of uptake of BDE-47 in KERTr after exposures to Pb and Cd. This study indicated that the uptake effects should be considered when performing risk assessment of human exposure to PBDEs and heavy metal. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: The present investigation documents the impact of tributyltin (TBT) on the ultrastructural variation of spermatogenesis in freshwater prawn Macrobrachium rosenbergii . The environmentally realistic concentration of TBT can cause damages to the endocrine and reproductive physiology of crustaceans. In this context, three concentrations viz. 10, 100, and 1000 ng/L were selected and exposed to prawns for 90 days. The TBT exposed prawn exhibited decrease the reproductive activity as evidenced by sperm count and sperm length compared to control. Histopathological results revealed the retarded testicular development, abnormal structure of seminiferous tubule, decrease in the concentration of spermatozoa, diminution of seminiferous tubule membrane, abundance of spermatocytes and vacuolation in testis of treated prawns. Ultrastructural study also confirmed the impairment of spermatogenesis in treated prawns. Furthermore, radioimmunoassay (RIA) clearly documented the reduction of testosterone level in TBT exposed groups. Thus, TBT substantially reduced the level of male sex hormone as well as biochemical constituents which ultimately led to impairment of spermatogenesis in the freshwater male prawn M.rosenbergii . © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Acrylamide is a proved toxin for testicular function, found in food when heated for long period of time. Green tea (Camellia sinensis) is a potent antioxidant; the aim of this study was to investigate the protective effect of green tea extract against the toxic effects of acrylamide in rat testes. Methods: acrylamide was administered orally to rats in different doses and also the extract of green tea was administered orally to different groups of animals in combination with the acrylamide. The weight of animals, testosterone hormone level and histopathological effect upon testicles were evaluated. Results: Testosterone hormone level in serum, and histopathological findings were significantly improved with the co-administration of green tea extract with the acrylamide. Green tea extract reversed all the toxic effects of acrylamide even in high dose for long period (90 days). Conclusion: Green tea extract is a potent antioxidant antidote for the acrylamide toxic effects upon testicular function. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Crude extract of Rheum palmatum L (CERP) has been used to treat different diseases in the Chinese population for decades. In this study, we investigated the effects of CERP on LS1034 human colorectal cancer cells in vitro and also examined possible mechanisms of cell death. Flow cytometric assays were used to measure the percentage of viable cells, cell cycle distribution including the sub-G1 phase (apoptosis), the activities of caspase-8, -9, and -3, reactive oxygen species (ROS) and Ca 2+ levels, and mitochondrial membrane potential (ΔΨ m ). DNA damage, nuclei condensation, protein expression, and translocation were examined by Comet assay, 4′-6-diamidino-2-phenylindole (DAPI) staining, Western blotting, and confocal laser system microscope, respectively. CERP induced apoptosis as seen by DNA fragmentation and DAPI staining in a concentration- and time-dependent manner in cancer cells. CERP was associated with an increase in the Bax/Bcl-2 protein ratio and CERP promoted the activities of caspase-8, -9, and -3. Both ROS and Ca 2+ levels were increased by CERP but the compound decreased levels of ΔΨ m in LS1034 cells. Laser confocal microscope also confirmed that CERP promoted the expressions of AIF, Endo G, cytochrome c, and GADD153 to induce apoptosis through mitochondrial-dependent pathway. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Previous studies in the wetland macrophyte Bidens laevis L have demonstrated that the insecticide endosulfan induces a high frequency of somatic chromosome aberrations in anaphase–telophase (CAAT) but no DNA changes as determined by the single cell gel electrophoresis (Comet) assay. Thus, cytogenetic biomarkers appear to be more sensitive to the toxic effects of the insecticide than the DNA molecule in the studied species. For this reason, the goals of this study were to use cytogenetic biomarkers—CAAT and abnormal metaphase—and defense biomarkers such as the activity of the antioxidant enzymes—guaiacol peroxidases (POD), glutathione reductase, and microsomal and cytosolic (m- and c-) glutathione- S -transferase (GST)—to evaluate in B. laevis effects caused by a commercial formulation of endosulfan. The frequency of CAAT was increased at 5, 10, 50, and 100 μg/L endosulfan with respect to the negative controls by 3.1, 2.5, 2.5, and 3.2-fold, respectively while the frequency of abnormal metaphases was also increased at the same concentrations by 3.5, 2.8, 3.2, and 11.3-fold, respectively. In addition to these aneugenic effects, other abnormalities such as C-mitosis and chromosome clumping were observed at 10 μg/L endosulfan. On the other hand, POD induction at 0.02, 0.5, 5, and 10 μg/L and m-GST inhibition at 0.5, 10, and 50 μg/L in plants exposed during 24 h to endosulfan were observed but all of these responses were highly variable. In conclusion, only cytogenetic biomarkers like CAAT in B. laevis can serve potentially as early warning systems to detect environmentally relevant concentrations of endosulfan in aquatic ecosystems. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT This study investigated the effects of waterborne chlorpyrifos with concentrations of 1 and 100 µg/L for L and H-groups, respectively, on metabolome profiles of carp plasma using 1 H-NMR. Principal component analysis suggests that chlorpyrifos exposure firstly affected in L and H-groups on day 2 or 4, and followed a second effect in both exposure groups on day 14. Levels of metabolites related to the energy production in the body, such as glucose, glycerol, valine, leucine, isoleucine, lactate, alanine, 3-D-hydroxybutyrates and acetoacetate, significantly changed by exposures of chlorpyrifos. Those results suggest that energy production was severely affected in carp. The exposure could also be highly elevated ammonia levels especially in H-group due to severe convulsion in muscle caused by the inhibition of acetylcholinesterase activity. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Sequelae of chronic lead (Pb 2+ ) toxicity includes anemia that is partially due to early death of erythrocytes characterized by excess accumulation of ROS and downregulation of antioxidant system causing oxidative stress and externalization of phosphatidylserine. In this study, pathophysiological based therapeutic application of garlic was evaluated against erythrocyte death. Results suggest that garlic administration prevents oxidative stress, restored the antioxidant balance in erythrocytes of Pb 2+ exposed mice. Moreover, in vitro studies revealed that activity of both scramblase and aminophospholipid translocase could be changed by modifying the critical sulfhydryl groups in presence of dithiothreitol during Pb 2+ exposure. Data also indicated that garlic treatment in Pb 2+ exposed mice exhibited sharp decline in PS exposure and increase in erythrocyte membrane thiol group followed by increase in aminophospholipid translocase activity and decline in scramblase activity. Findings indicated that garlic has the ability to restore the lifespan of erythrocytes during Pb 2+ exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Thallium(I) is a highly toxic heavy metal; however, up to now, its mechanisms are poorly understood. The authors' previous studies showed that this compound could induce reactive oxygen species (ROS) formation, reduced glutathione (GSH) oxidation, membrane lipid peroxidation, and mitochondrial membrane potential (MMP) collapse in isolated rat hepatocyte. Because the liver is the storage site of thallium, it seems that the liver mitochondria are one of the important targets for hepatotoxicity. In this investigation, the effects of thallium on mitochondria were studied to investigate its mechanisms of toxicity. Mitochondria were isolated from rat liver and incubated with different concentrations of thallium (25–200 µM). Thallium(I)-treated mitochondria showed a marked elevation in oxidative stress parameters accompanied by MMP collapse when compared with the control group. These results showed that different concentrations of thallium (25–200 µM) induced a significant ( P  〈 0.05) increase in mitochondrial ROS formation, ATP depletion, GSH oxidation, mitochondrial outer membrane rupture, mitochondrial swelling, MMP collapse, and cytochrome c release. In general, these data strongly supported that the thallium(I)-induced liver toxicity is a result of the disruptive effect of this metal on the mitochondrial respiratory complexes (I, II, and IV), which are the obvious causes of metal-induced ROS formation and ATP depletion. The latter two events, in turn, trigger cell death signaling via opening of mitochondrial permeability transition pore and cytochrome c expulsion. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT The acute toxicity of cylindrospermopsin (CYN) has been established in rodents, based on diverse intraperitoneal an oral exposure studies and more recently in fish. But no data have been reported in fish after subchronic exposure to cyanobacterial cells containing this cyanotoxin, so far. In this work, tilapia ( Oreochromis niloticus ) were exposed by immersion to lyophilized Aphanizomenon ovalisporum cells added to the aquaria using two concentration levels of CYN (10 or 100 μg CYN L −1 ) and deoxy-cylindrospermopsin (deoxy-CYN) (0.46 or 4.6 μg deoxy-CYN L −1 ), during two different exposure times: 7 or 14 d. This is the first study showing damage in the liver, kidney, hearth, intestines, and gills of tilapia after subchronic exposure to cyanobacterial cells at environmental relevant concentrations. The major histological changes observed were degenerative processes and steatosis in the liver, membranous glomerulopathy in the kidney, myofibrolysis and edema in the heart, necrotic enteritis in the gastrointestinal tract, and hyperemic processes in gill lamellae and microhemorrhages. Moreover, these histopathological findings confirm that the extent of damage is related to the CYN concentration and length of exposure. Results from the morphometric study indicated that the average of nuclear diameter of hepatocytes and cross-sections of proximal and distal convoluted tubules are useful to evaluate the damage induced by CYN in the main targets of toxicity. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Phoxim ( O , O -diethyl O -(alpha-cyanobenzylideneamino) phosphorothioate) is a powerful organophosphorus pesticide with high potential for Bombyx mori larvae of silkworm exposure. However, it is possible that during the phoxim metabolism, there is generation of reactive oxygen species (ROS) and phoxim may produce oxidative stress and neurotoxicity in an intoxicated silkworm. Titanium dioxide nanoparticles (TiO 2 NPs) pretreatment has been demonstrated to increase antioxidant capacity and acetylcholinesterase (AChE) activity in organisms. This study was, therefore, undertaken to determine phoxim-induced oxidative stress and neurotoxicity to determine whether phoxim intoxication alters the antioxidant system and AChE activity in the B. mori larval midgut, and to determine whether TiO 2 NPs pretreatment attenuates phoxim-induced toxicity. The findings suggested that phoxim exposure decreased survival of B. mori larvae, increased malondialdehyde (MDA), carbonyl and 8-OHdG levels, and ROS accumulation in the midgut. Furthermore, phoxim significantly decreased the activities of AChE, superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione- S -transferase (GST), and levels of ascorbic acid (AsA), reduced glutathione (GSH), and thiol in the midgut. TiO 2 pretreatment, however, could increase AChE activity, and remove ROS via activating SOD, CAT, APX, GR, and GST, and accelerating AsA–GSH cycle, thus attenuated lipid, protein, and DNA peroxidation and improve B. mori larval survival under phoxim-induced toxicity. Moreover, this experimental system would help nanomaterials to be applied in the sericulture. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT This study was designed to investigate the possibility of β-cyfluthrin to induce oxidative stress and biochemical perturbations in rat liver and the role of selenium in alleviating its toxic effects. Male Wister rats were randomly divided into four groups of seven each, group I served as control, group II treated with selenium (200 µg/kg BW), group III received β-cyfluthrin (15 mg/kg BW, 1/25 LD 50 ), and group IV treated with β-cyfluthrin plus selenium. Rats were orally administered their respective doses daily for 30 days. The administration of β-cyfluthrin caused elevation in lipid peroxidation (LPO) and reduction in the activities of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), glutathione S -transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GR). A decrease in reduced glutathione (GSH) content was also observed. Liver aminotransferases (AST and ALT) and alkaline phosphatase (ALP) were decreased, whereas lactate dehydrogenase (LDH) was increased. Selenium in β-cyfluthrin-induced liver oxidative injury of the rats modulated LPO, CAT, SOD, GSH, GST, GPx, and GR. Also, liver AST, ALT, ALP, and LDH were maintained near normal level due to selenium treatment. It is concluded that selenium scavenges reactive oxygen species and render a protective effect against β-cyfluthrin toxicity. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Ambient air pollutants have been reported to induce oxidative stress based inflammatory responses in humans and experimental animals. However, most of these reports describe the actions of the particulate phase of ambient and exhaust samples. We describe here results of studies investigating the actions of the vapor phase of ambient air samples collected in the midtown area of Los Angeles on human bronchial epithelial BEAS-2B cells using DNA microarray analysis. Among 26 genes whose expression increased fourfold or more, four genes were associated with detoxifying genes regulated by the transcription factor Nrf2. Consistent with these results, the vapor samples activate the Nrf2-ARE pathway, resulting in up-regulation of heme oxygenase-1 (HO-1), glutamate cysteine ligase modifier subunit, and cystine transporter (xCT) mRNA and proteins. No appreciable increases in pro-inflammatory genes were observed. These results suggest that ambient vapor samples activate the Nrf2-ARE pathway but not an inflammatory response. Also, treatment of the vapor samples with glutathione resulted in reduction in the Nrf2 activation and HO-1 induction, suggesting that electrophiles in vapor samples contribute to this Nrf2-dependent antioxidant or adaptive response.

Description: ABSTRACT Diatoms are sensitive indicators of water quality, and hence used for environmental hazard assessments; however, their toxicogenomic studies have been insufficiently attempted. In the present study, we determined the cDNA sequence of heat shock protein 20 ( Hsp20 ) gene from the diatom Ditylum brightwellii , and examined the transcriptional responses of the gene after exposing it to environmental stressors such as thermal shock, metals, and endocrine-disrupting chemicals (EDCs). The open reading frame (ORF) of DbHsp20 was 531 bp long, encoding 177 amino acid residues (19.49 kDa) with a conserved C-terminal and α-crystallin domain. The genomic region of DbHsp20 did not contain introns. Phylogeny of eukaryotic Hsp20s showed D . brightwellii was closely related to other diatoms. With regard to the gene expressional profile, real-time PCR results showed that the gene was significantly upregulated ( P  〈 0.001) under thermal stress, with the highest change of 3.2-fold. Metals' (copper and nickel) treatments showed that it was induced after a certain point of treated concentration. On the contrary, EDCs did not display noticeable change on the expression of DbHsp20 . These results suggest that the diatom Hsp20 basically responds to thermal stress, but may differentially respond to toxic substances such as metals and organic compounds such as EDCs. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT The risk presented by β-blockers on aquatic organisms remains uncertain, particularly given the enantiospecific differences in toxicity of chiral β-blockers. In this study, the toxicity of two β-blockers, propranolol and metoprolol, was determined. The 96-h LC 50 of propranolol in the zebrafish larvae was 2.48 mg/L, whereas 50 mg/L metoprolol did not result in death. Both β-blockers decreased the heart rate and hatching rate and increased the mortality of the zebrafish embryos. Among these indicators, the heart rate was the most sensitive. However, the acute larval and embryo toxicity results displayed no enantioselectivity. Additionally, the transcriptional response of the genes encoding the β-adrenergic receptors and those involved in other physiological processes, including the antioxidant response, detoxification, and apoptosis, in zebrafish larvae exposed to the β-blockers was examined. Although the changes in gene transcription were fairly minor, significant enantioselectivity was observed for β-blockers, suggesting that the transcriptional response was more sensitive for the evaluation of enantiospecific toxicity. Based on these results, the pharmaceutical drugs were not expected to pose a risk to fish; however, this conclusion should not be considered final. These results also demonstrated that the enantiospecific toxicity of chiral β-blockers should be investigated when performing an ecological risk assessment. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: In this study, endothelial nitric oxide synthase activity and nitric oxide (NO) production by human erythrocytes in the presence and absence of mercuric chloride (HgCl 2 ), L -arginine ( L -ARG), N ω -nitro- L -arginine methyl ester ( L -NAME), and naringin (NAR) were investigated. In addition, the levels of reduced glutathione (GSH) and related enzymes were estimated in erythrocytes hemolysate. The protein carbonyl content (PCC) and thiobarbituric acid-reactive substances (TBARS) levels were also determined. The results of this study revealed that the treatment of erythrocytes with either HgCl 2 or L -NAME induced a significant decrease in NOS activity and nitrite levels compared with control cells. Furthermore, mercury exposure significantly increased the levels of PCC and TBARS but reduced the GSH level. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and glutathione- S -transferase (GST) were inhibited. The exposure of erythrocytes to HgCl 2 in combination with L -ARG, NAR, or both ameliorated the investigated parameters compared with erythrocytes incubated with HgCl 2 alone. These results indicate that mercury exposure decreased both erythrocyte NOS activity and nitrite production, and that these parameters might be indicative of mercury exposure. The data also suggest that concomitant treatment with NAR can restore NO bioavailability through either its metal-chelating properties or its antioxidant activity.

Description: ABSTRACT Divalent lead ions (Pb 2+ ) are toxic environmental pollutants known to cause serious health problems in humans and animals. Absorption of Pb 2+ from air, water, and food takes place in the respiratory and digestive tracts. The ways in which absorbed Pb 2+ affects cell physiology are just beginning to be understood at the molecular level. Here, we used reverse transcription PCR and Western blotting to analyze cultures of human gastric carcinoma cells exposed to 10 μM lead nitrate. We found that Pb 2+ induces gastrin hormone gene transcription and translation in a time-dependent manner. Promoter deletion analysis revealed that activator protein 1 (AP1) was necessary for gastrin gene transcription in cells exposed to Pb 2+ . MitogIen-activated protein kinase (MAPK)/ERK kinase inhibitor PD98059 suppressed the Pb 2+ -induced increase in messenger RNA. Epidermal growth factor receptor (EGFR) inhibitors AG1478 and PD153035 reduced both transcription and phosphorylation by extracellular signal-regulated kinase (ERK1/2). Cells exposed to Pb 2+ also increased production of c-Jun protein, a component of AP1, and over-expression of c-Jun enhanced activation of the gastrin promoter. In sum, the findings suggest the EGFR-ERK1/2-AP1 pathway mediates the effects of Pb 2+ on gastrin gene activity in cell culture. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Present study was focused on evaluation of a semiquinone glucoside derivative (SQGD) isolated from radioresistant bacterium Bacillus sp. INM-1 for its ability against γ radiation induced oxidative stress in irradiated mice. Animals were divided into four group, i.e., (i) untreated control mice; (ii) SQGD treated (50 mg/kg b. wt. i.p.) mice; (iii) irradiated (10 Gy) mice; and (iv) irradiated mice which were pre-treated (−2 h) with SQGD (50 mg/kg b. wt. i.p.). Following treatment, liver homogenates of the treated mice were subjected to endogenous antioxidant enzymes estimation. Result indicated that SQGD pre-treatment, significantly ( P 〈 0.05) induced superoxide dismutase (SOD) (19.84 ± 2.18% at 72 h), catalase (CAT) (26.47 ± 3.11% at 12 h), glutathione (33.81 ± 1.99% at 24 h), and glutathione- S -transferase (24.40 ± 2.65% at 6 h) activities in the liver of mice as compared with untreated control. Significant ( P 〈 0.05) induction in SOD (50.04 ± 5.59% at 12 h), CAT (62.22 ± 7.50 at 72 h), glutathione (42.92 ± 2.28% at 24 h), and glutathione- S -transferase (46.65 ± 3.25 at 12 h) was observed in irradiated mice which were pre-treated with SQGD compared with only irradiated mice. Further, significant induction in ABTS + radicals (directly proportional to decrease mM Trolox equivalent) was observed in liver homogenate of H 2 O 2 treated mice which were found to be significantly inhibited in H 2 O 2 treated mice pre-treated with SQGD. Thus, it can be concluded that SQGD treatment neutralizes oxidative stress caused by irradiation not only by enhancing endogenous antioxidant enzymes but also by improving total antioxidant status of cellular system and thus cumulative effect of the phenomenon may contributes to radioprotection. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT: Due to advent of nanotechnology, nickel nanoparticles (Ni NPs) are increasingly recognized for their utility in various applications including catalysts, sensors and electronics. However, the environmental and human health effects of Ni NPs have not been fully investigated. In this study, we examined toxic effects of Ni NPs in human liver (HepG2) cells. Ni NPs were prepared and characterized by X-ray diffraction, transmission electron microscopy and dynamic light scattering. We observed that Ni NPs (size, ∼28 nm; concentration range, 25–100 μg/mL) induced cytotoxicity in HepG2 cells and degree of induction was concentration-dependent. Ni NPs were also found to induce oxidative stress in dose-dependent manner evident by induction of reactive oxygen species and depletion of glutathione. Cell cycle analysis of cells treated with Ni NPs exhibited significant increase of apoptotic cell population in subG1 phase. Ni NPs also induced caspase-3 enzyme activity and apoptotic DNA fragmentation. Upregulation of cell cycle checkpoint gene p53 and bax/bcl-2 ratio with a concomitant loss in mitochondrial membrane potential suggested that Ni NPs induced apoptosis in HepG2 cells was mediated through mitochondrial pathway. This study warrants that applications of Ni NPs should be carefully assessed as to their toxicity to human health. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Benzene-induced erythropoietic depression has been proposed to be due to the production of toxic metabolites. Presently, the cytotoxicities of benzene metabolites, including phenol, catechol, hydroquinone, and 1,2,4-benzenetriol, to erythroid progenitor-like K562 cells were investigated. After exposure to these metabolites, K562 cells showed significant inhibition of viability and apoptotic characteristics. Each metabolite caused a significant increase in activities of caspase-3, -8, and -9, and pretreatment with caspase-3, -8, and -9 inhibitors significantly inhibited benzene metabolites-induced phosphatidylserine exposure. These metabolites also elevated expression of Fas and FasL on the cell surface. After exposure to benzene metabolites, K562 cells showed an increase in reactive oxygen species level, and pretreatment with N -acetyl- l -cysteine significantly protected against the cytotoxicity of each metabolite. Interestingly, the control K562 cells and the phenol-exposed cells aggregated together, but the cells exposed to other metabolites were scattered. Further analysis showed that hydroquione, catechol, and 1,2,4-benzenetriol induced a decrease in the cell surface sialic acid levels and an increase in the cell surface sialidase activity, but phenol did not cause any changes in sialic acid levels and sialidase activity. Consistently, an increase in expression level of sialidase Neu3 mRNA and a decrease in mRNA level of sialyltransferase ST3GAL3 gene were detected in hydroquione-, catechol-, or 1,2,4-benzenetriol-treated cells, but no change in mRNA levels of two genes were found in phenol-treated cells. In conclusion, these benzene metabolites could induce apoptosis of K562 cells mainly through caspase-8-dependent pathway and ROS production, and sialic acid metabolism might play a role in the apoptotic process. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT This paper presents an evaluation of the genotoxic effects of cadmium chloride (CdCl 2 ) on marine gastropod, Nerita chamaeleon following the technique of comet assay and the DNA alkaline unwinding assay (DAUA). In this study, the extent of DNA damage in gill cells of N. chamaeleon was measured after in vivo exposure to four different concentrations (10, 25, 50, and 75 µg/L) of CdCl 2 . In vitro exposure of hydrogen peroxide (H 2 O 2 ; 1, 10, 25, and 50 µM) of the gill cells showed a significant increase in the percentage tail DNA, Olive tail moment, and tail length (TL). Significant changes in percentage tail DNA by CdCl 2 exposure were observed in all exposed groups of snails with respect to those in control. Exposure to 75 µg/L of CdCl 2 produced significant decrease in DNA integrity as measured by DAUA at all duration with respect to control. In vivo exposure to different concentrations of CdCl 2 (10, 25, 50, and 75 µg/L) to N. chamaeleon showed considerable increase in DNA damage as observed by both alkaline comet assay and the DAUA. The extent of DNA damage in marine gastropods determined by the application of alkaline comet assay and DAUA clearly indicated the genotoxic responses of marine gastropod, N. chamaeleon to a wide range of cadmium concentration in the marine environment. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Hexabromobenzene (HBB) is a novel brominated flame retardant (BFR) with ample evidence of its ubiquitous existence in the aquatic ecosystems. However, to date, the toxicological effects of this BFR on fish have been inadequately researched. The present study was conducted, based on an in vivo model, to investigate HBB-induced biochemical changes in liver and gill tissues of Carassius auratus after medium-term exposure to different concentrations (10, 150, and 300 mg/kg) for 7, 14, and 25 days. Oxidative stress was evoked evidently for the prolonged exposure, demonstrated by significant inhibition in antioxidant enzymes activities including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and glutathione S-transferase, and a decrease in reduced glutathione level, as well as simultaneous elevation in malondialdehyde content. Moreover, Na + , K + -ATPase activity, and protein level were remarkably reduced in fish tissues. Based on the integrated biomarker response, the toxic potency in each treatment was distinguished, and the more severe stress was mainly noted with the increasing concentrations and the extending durations. It was also observed that liver exhibited more pronounced alterations in biochemical parameters than gill, probably indicating the vulnerability of liver to HBB-triggered oxidative stress. Taken together, the results of this study clearly showed that HBB was capable of inducing oxidative stress and inhibiting Na + , K + -ATPase activity in different tissues of C. auratus after medium-term exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Silver nanoparticles are increasingly used in various products, due to their antibacterial properties. Despite its wide spread use, only little information on possible adverse health effects exists. Therefore, the aim of this study was to assess the toxic potential of silver nanoparticles (〈100 nm) in human lung epithelial (A549) cells and the underlying mechanism of its cellular toxicity. Silver nanoparticles induced dose and time-dependent cytotoxicity in A549 cells demonstrated by MTT and LDH assays. Silver nanoparticles were also found to induce oxidative stress in dose and time-dependent manner indicated by depletion of GSH and induction of ROS, LPO, SOD, and catalase. Further, the activities of caspases and the level of proinflammatory cytokines, namely interleukin-1β (IL-1β) and interleukin-6 (IL-6) were significantly higher in treated cells. DNA damage, as measured by single cell gel electrophoresis, was also dose and time-dependent signicants in A549 cells. This study investigating the effects of silver nanoparticles in human lung epithelial cells has provided valuable insights into the mechanism of potential toxicity induced by silver nanoparticles and warrants more careful assessment of silver nanoparticles before their industrial applications. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT We have recently demonstrated that exposure to barium for a short time (≤4 days) and at a low level (5 µM = 687 µg/L) promotes invasion of human nontumorigenic HaCaT cells, which have characteristics similar to those of normal keratinocytes, suggesting that exposure to barium for a short time enhances malignant characteristics. Here we examined the effect of exposure to low level of barium for a long time, a condition mimicking the exposure to barium through well water, on malignant characteristics of HaCaT keratinocytes. Constitutive invasion activity, focal adhesion kinase (FAK) protein expression and activity, and matrix metalloproteinase 14 (MMP14) protein expression in primary cultured normal human epidermal keratinocytes, HaCaT keratinocytes, and HSC5 and A431 human squamous cell carcinoma cells were augmented following an increase in malignancy grade of the cells. Constitutive invasion activity, FAK phosphorylation, and MMP14 expression levels of HaCaT keratinocytes after treatment with 5 µM barium for 4 months were significantly higher than those of control untreated HaCaT keratinocytes. Taken together, our results suggest that exposure to a low level of barium for a long time enhances constitutive malignant characteristics of HaCaT keratinocytes via regulatory molecules (FAK and MMP14) for invasion. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Di(2-ethylhexyl) phthalate (DEHP) and polychlorinated biphenyls (PCBs) are two widely distributed pollutants that are of great concern due to their adverse health effects. However, few studies have investigated the combined effects of DEHP and PCBs. In this study, adult mice were continuously exposed to mixtures of DEHP (15 mg/kg bodyweight/day) and Aroclor 1254 (7.5 mg/kg bodyweight/day) for 12 days to investigate the combined effects of these compounds. The results showed that the ratio of the liver weight to the body weight was higher in the treated group than that in the control group. The effects of combined exposure on three important receptors, the proliferator-activated receptor (PPAR), estrogen receptor (ER), and aryl hydrocarbon receptor (AHR), were investigated. The mRNA level of PPARγ was significantly up-regulated after exposure. The expression level of ERα was decreased in the male treated group. In contrast, the expression levels of AHR and related genes (cyp1a1 and cyp1b1) were not markedly affected. The expression level of phospholipase A (PLA) was significantly down-regulated at both the mRNA and protein levels in male mice after combined treatment. In all, our study demonstrated the combined effects of DEHP and PCBs on the expression levels of key receptors in mice. The combined exposure led to a decrease in phospholipase in male mice. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Inorganic copper, such as that in drinking water and copper supplements, largely bypasses the liver and enters the free copper pool of the blood directly and that promote immunosuppression. According to our previous in vivo report, we evaluate the details of the apoptotic mechanism in liver, we have investigated how copper regulates apoptotic pathways in liver. We have analyzed different protein expression by Western blotting and immunohistochemistry expression. We have also have measured mitochondrial trans-membrane potential, Annexin V assay, ROS, and CD4 + and CD8 + population in hepatocyte cells by flow cytometry. Copper-treated mice evidenced immunotoxicity as indicated by dose-related, distinct histomorphological changes in liver. Flow cytometric analyses revealed a dose-related increase in the percentages of hepatocyte cells in the Sub-G0/G1 state, further confirmed by Annexin V binding assay. In addition, the copper treatments altered the expression of apoptotic markers, further ROS generation and mitochondrial trans-membrane potential changes promote intrinsic pathway of apoptosis that was p53 independent. Apart from the role of inflammation, our findings also have identified the role of other partially responsible apoptotic molecules p73 that differentially changed due to copper treatment. Our study demonstrates how apoptotic pathways regulate copper-induced immunosuppression in liver. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT In this study, Artemia salina (crustacean filter feeders) larvae were used as a test model to investigate the toxicity of aluminum oxide nanoparticles (Al 2 O 3 NPs) on marine microorganisms. The uptake, toxicity, and elimination of α-Al 2 O 3 (50 nm and 3.5 μm) and γ-Al 2 O 3 (5 nm and 0.4 μm) NPs were studied. Twenty-four and ninety-six hour exposures of different concentrations of Al 2 O 3 NPs to Artemia larvae were conducted in a seawater medium. When suspended in water, Al 2 O 3 NPs aggregated substantially with the sizes ranging from 6.3 nm to 〉0.3 µm for spherical NPs and from 250 to 756 nm for rod-shaped NPs. The phase contrast microscope images showed that NPs deposited inside the guts as aggregates. Inductively coupled plasma mass spectrometry analysis showed that large particles (3.5 μm α-Al 2 O 3 ) were not taken up by Artemia , whereas fine NPs (0.4 μm γ-Al 2 O 3 ) and ultra-fine NPs (5 nm γ-Al 2 O 3 and 50 nm α-Al 2 O 3 ) accumulated substantially. Differences in toxicity were detected as changing with NP size and morphology. The malondialdehyde levels indicated that smaller γ-Al 2 O 3 (5 nm) NPs were more toxic than larger γ-Al 2 O 3 (0.4 µm) particulates in 96 h. The highest mortality was measured as 34% in 96 h for γ-Al 2 O 3 NPs (5 nm) at 100 mg/L (LC 50 〉 100 mg/L). γ-Al 2 O 3 NPs were more toxic than α-Al 2 O 3 NPs at all conditions. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Chlorpyrifos (CPF) is the widely used organophosphate pesticide in agriculture throughout the world. It has been found that CPF is relatively safe to human but highly toxic to fish. In this study, acute toxicity of CPF on goldfish was determined and then the transcription of goldfish cytochrome P450 (CYP) 3A was evaluated after 96 h of CPF exposure at concentrations of 15.3 [1/10 50% lethal concentration (LC 50 )] or 51 μg L −1 (1/3 LC 50 ) of CPF. Meanwhile, the enzymatic activities of acetylcholinesterase (AChE), superoxide dismutase (SOD), and catalase (CAT), total antioxidant activity (T-AOC), and the contents of malondialdehyde (MDA) in the liver or brain of goldfish were also determined. The results of acute toxicity testing showed that the 96-h LC 50 of CPF to the goldfish was 153 μg L −1 . Moreover, a length sequence of 1243 bp CYP3A cDNA encoding for 413 amino acids from goldfish liver was cloned. Polymerase chain reaction results reveal that CPF exposure downregulates CYP 3A transcription in goldfish liver, suggesting that goldfish CYP 3A may be not involved in CPF bioactivation. Finally, the results of biochemical assays indicate that 96 h of CPF exposure remarkably inhibits AChE activity in fish liver or brain, alters hepatic antioxidant enzyme activities, decreases brain T-AOC, and causes lipid peroxidation in fish liver. These results suggest that oxidative stress might be involved in CPF toxicity on goldfish. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Human exposure to persistent organic pollutants (POPs) is a certainty, even to long banned pesticides like o,p ′-dichlorodiphenyltrichloroethane ( o,p ′-DDT), and its metabolites p,p ′-dichlorodiphenyldichloroethylene ( p,p ′-DDE), and p,p ′-dichlorodiphenyldichloroethane ( p,p ′-DDD). POPs are known to be particularly toxic and have been associated with endocrine-disrupting effects in several mammals, including humans even at very low doses. As environmental estrogens, they could play a critical role in carcinogenesis, such as in breast cancer. With the purpose of evaluating their effect on breast cancer biology, o,p ′-DDT, p,p ′-DDE, and p,p ′-DDD (50–1000 nM) were tested on two human breast adenocarcinoma cell lines: MCF-7 expressing estrogen receptor (ER) α and MDA-MB-231 negative for ERα, regarding cell proliferation and viability in addition to their invasive potential. Cell proliferation and viability were not equally affected by these compounds. In MCF-7 cells, the compounds were able to decrease cell proliferation and viability. On the other hand, no evident response was observed in treated MDA-MB-231 cells. Concerning the invasive potential, the less invasive cell line, MCF-7, had its invasion potential significantly induced, while the more invasive cell line MDA-MB-231, had its invasion potential dramatically reduced in the presence of the tested compounds. Altogether, the results showed that these compounds were able to modulate several cancer-related processes, namely in breast cancer cell lines, and underline the relevance of POP exposure to the risk of cancer development and progression, unraveling distinct pathways of action of these compounds on tumor cell biology. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Exposure to endocrine disruptors (EDs) during early development might lead to adverse health outcomes later in life. Tributyltin (TBT), a proven ED, is widely used in consumer goods and industrial products. Herein we demonstrate the effects of low doses of tributyltin chloride (TBTCl) on reproduction of male KM mice. Pregnant mice were administered by gavage with 0, 1, 10, or 100 μg TBTCl/kg body weight/day from day 6 of pregnancy through the period of lactation. TBTCl dramatically decreased sperm counts and motility on postnatal days (PNDs) 49 and 152. Meanwhile, a significant increase in sperm abnormality was observed in exposed mice on PND 49, but comparable to that in the control on PND 152. The histopathological analysis of testes of treated animals showed a dose-dependent increase in sloughing of germ cells in seminiferous tubules. Mice treated with 10 μ g TBTCl/kg exhibited decreased intratesticular 17β-estradiol (E2) levels on PND 49, and then followed by an obvious recovery on PND 152. While, no significant differences in serum E2, testosterone (T) levels and intratesticular T levels were detectable between control and TBTCl-exposed offspring at the sacrifice. These results suggest that perinatal TBTCl exposure is implicated in causing long lasting alterations in male reproductive system and these changes may persist far into adulthood. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT T-2 toxin is the most toxic among mycotoxins and poses a potential health hazard for both humans and animals. At high doses, T-2 toxin can cause shock-like syndrome that can result in death. We evaluated the effect of time course and route of exposure on hepatic oxidative damage in mice and it is only such study so far to compare the effects of dermal and subcutaneous exposure of T-2 toxin. Mice were exposed to 1 LD50 of T-2 toxin either by percutaneous (5.94 mg/kg body weight) or subcutaneous (1.54 mg/kg body weight) route and sacrificed at 0, 1, 3, and 7 days postexposure. Analysis of a number of serum biochemical variables, antioxidant enzymes activity, gene and protein expression by immunoblot assay showed time and route dependent effects of T-2 induced hepatic oxidative damage. Time dependent increase in protein carbonyl content and protein oxidation was seen in serum and liver. Results of our study may provide possible mechanism for developing medical countermeasures against T-2 toxin. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Triclosan (TCS) is considered a potent endocrine disruptor that causes reproductive toxicity in non-mammals, but it is still unclear exactly whether TCS has adverse effects on the sperm or reproductive organs in mammals. In this study, we aimed to evaluate the distribution status of TCS in male reproductive organs of rats, and seek the correlation with the TCS-induced sperm toxicity or reproductive organ damage. Male rats were intragastrically administered with TCS at a dose of 50 mg/kg, the kinetics of TCS in the plasma and reproductive organs were investigated. TCS in testes and prostates both showed a lower-level distritbution compared to that in the plasma, which indicates it has no tendency to accumulate in those organs. However, TCS in the epididymides showed a longer elimination half-life ( t 1/2z ), a longer the mean retention time (MRT), and a lower clearance (CL Z /F) compared with those in the plasma. Besides, the ratios of mean area under the concentration-time curve (AUC) 0–96h(epididymides/plasma) and AUC 0–∞(epididymides/plasma) were 1.13 and 1.51, respectively. These kinetic parameters suggest TCS has an accumulation tendency in the epididymides. Based on this, we investigated the TCS-induced sperm toxicity and histopathological changes of reproductive organs in rats. TCS was given intragastrically at doses of 10, 50, and 200 mg/kg for 8 weeks. Rats treated with the high dose (200 mg/kg) of TCS showed a significant decrease in daily sperm production (DSP), changes in sperm morphology and epididymal histopathology. Considering the histopathological change in the epididymides, TCS may induce the epididymal damage due to the epididymal accumulation of that. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT The impact of simultaneously elevated serum ferritin and mercury concentrations on hypertension in the general population is not known. To determine the association of serum ferritin and mercury concentrations with hypertension, 6213 subjects (3060 men and 3153 women) over 20 years of age from 2008 to 2010 Korea National Health and Nutrition Examination Survey were divided into tertiles according to serum ferritin and mercury concentrations in each gender. Serum ferritin (258.2 vs. 94.8 pmol/L) and mercury concentrations (28.4 vs. 19.9 nmol/L) were higher in men than in women. Serum ferritin (men; P = 0.029, women; P 〈 0.001) and mercury (men; P 〈 0.001, women; P = 0.003) concentrations were significantly associated with the prevalence of hypertension. In addition, significant correlation between serum ferritin and mercury concentrations in both men ( r = 0.193, P 〈 0.001) and women ( r = 0.145, P 〈 0.001) were found. Also, the increase of serum ferritin concentrations were more prominent in men ( P 〈 0.001) than in women ( P = 0.017) as the serum mercury tertiles increased after proper adjustments. Furthermore, significantly higher odds ratios of hypertension were found in the second (OR = 1.86, 95% CI; 1.05–3.30), and third (OR = 1.84, 95% CI; 1.01–3.36) tertiles of serum ferritin with the top tertile of serum mercury in men. The current study indicate that serum ferritin and mercury concentrations are associated with the prevalence of hypertension and that simultaneously elevated serum ferritin and mercury concentrations are related to the risk for hypertension in men. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Previously, we have reported alterations to HSP27 during Microcystin-LR (MC-LR)-induced cytoskeletal reorganization in the human liver cell line HL7702. To further elucidate the detailed mechanism of MC-LR-induced cytoskeletal assembly, we focused on two cytoskeletal-related proteins, Tau and VASP. These two proteins phosphorylated status influences their ability to bind and stabilize cytoskeleton. We found that MC-LR markedly increased the level of Tau phosphorylation with the dissociation of phosphorylated Tau from the cytoskeleton. Furthermore, the phosphorylation of Tau induced by MC-LR was suppressed by an activator of PP2A and by an inhibitor of p38 MAPK. VASP was also hyperphosphorylated upon MC-LR exposure; however, its phosphorylation appeared to regulate its cellular localization rather than cytoskeletal dynamics, and its phosphorylation was unaffected by the PP2A activator. These data suggest that phosphorylated Tau is regulated by p38 MAPK, possibly as a consequence of PP2A inhibition. Tau hyperphosphorylation is likely an important factor leading to the cytoskeletal destabilization triggered by MC-LR and the role of VASP alteration upon MC-LR exposure needs to be studied further. To our knowledge, the finding that Tau is implicated in cytoskeletal destabilization in MC-LR-treated hepatocytes and MC-LR-induced VASP's alteration has not been reported previously. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Metastasis plays an important role in mortality of cancer patients. Migration and invasion are the major characteristics of tumor metastasis. The induction of matrix metalloproteinases (MMPs) such as MMP-2 and -9 are particularly important for the invasiveness of various cancer cells. Bufalin, a class of toxic steroids, was purified from the skin glands of Bufo gargarizans or Bufo melanostictus ; it is known to inhibit proliferation of human cancer cells. In this study, we investigated the antiinvasive mechanisms of bufalin in the human hepatocellular cancer cell line SK-Hep1. Bufalin significantly reduced serum-induced cell invasion and migration. Furthermore, bufalin markedly inhibited MMP-2 and -9 activity, mRNA expression and protein levels in SK-Hep1 cells. Bufalin attenuated phosphoinisitide-3-kinase (PI3K) and phosphorylation of AKT which was associated with reduced levels of nuclear factor kappa B (NF-κB). Bufalin also suppressed protein levels of FAK and Rho A, VEGF, MEKK3, MKK7, and uPA and it diminished NF-κB translocation. Based on these observations, we propose that bufalin is acts as an antiinvasive agent by inhibiting MMP-2 and -9 and involving PI3K/AKT and NF-κB pathways. Bufalin is a potential therapeutic agent that may have efficacy in preventing the invasion and metastasis of malignant liver tumors. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Osteosarcoma is the most common primary malignancy of the bone cancers. In the Chinese population, the crude extract of Corni Fructus (CECF) has been used as Traditional Chinese medicine to treat several different diseases for hundreds of years. In the present study, effects of CECF on inhibition of migration and invasion in U-2 OS human osteosarcoma cells were examined. CECF significantly inhibited migration and invasion of U-2 OS human osteosarcoma cells. We also found that CECF inhibited activities of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9). CECF decreased protein levels of FAK, PKC, SOS1, MKK7, MEKK3, GRB2, NF-κB p65, COX-2, HIF-1α, PI3K, Rho A, ROCK-1, IRE-1α, p-JNK1/2, p-ERK1/2, p-p38, Ras, p-PERK, MMP-2, MMP-9, and VEGF in U-2 OS cells. Results of this study indicate that CECF may have potential as a novel anticancer agent for the treatment of osteosarcoma by inhibiting migration and invasion of cancer cells © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT The objective of this study was to assess whether subchronic exposure to benzo(a)pyrene (BaP) via oral ingestion alter endpoints of the reproductive system of mice. Hsd: ICR (CD1) 10-week-old males ( n = 8) were randomly assigned to the exposure group and control group. Mice were administered BaP for 30 and 60 days by daily gavage at doses of 1, 10, 50, and 100 mg/kg body weight per day. At the end of the experiments, mice were anesthetized and reproductive organs, including testes, seminal vesicles, prostate, and cauda epididymis, were removed and examined. Spermatozoa quality and DNA strand breaks were assessed—1 and 10 mg/kg/day of BaP for 30 and 60 days did not significantly induce altered morphology or weights of testes, prostate, seminal vesicle, and epididymis, and spermatozoa quality of mice; 100 mg/kg/day of BaP for 60 days decreased weights of testes, seminal vesicle, and cauda epididymis. BaP exposure also significantly decreased motility, normal head morphology, vitality, and concentration of mature spermatozoa. In addition, BaP exposure induced a significant increase in DNA strand breaks. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Pyrethroids are known to be neurotoxic. However, their toxic effects including that of allethrin on the male reproductive tract are not elucidated. Adult male rats were treated orally with 25, 50, 100, and 150 mg/kg body weight allethrin every day for 60 days. Lipid peroxidation was increased ( p  〈 0.001) in the caput, cauda, and testes. Nitric oxide production was increased ( p  〈 0.001) in the caput, but unaltered in the cauda and testes. The activities of catalase, glutathione peroxidase, glutathione- S -transferase, and superoxide dismutase were decreased in the caput and cauda where as a decrease was observed in the testis obtained from allethrin treated rats. In the epididymides and testes, damage to tubular architecture, congestion, degeneration of epithelial cell lining, intestinal edema, and presence of dead or degenerating spermatids were observed in a dose dependent manner. The expression profile of genes involved in spermatogenesis ( Tgf-beta1 ), sperm maturation ( Spag11e ), and sperm function ( Defb22 ) were reduced ( p  〈 0.001) in allethrin rats. The expression of p53 gene was decreased and increased phosphorylation of MAPK (p42/p44) expression was observed the male reproductive tract tissues of allethrin treated rats. Although earlier studies have reported the effects of allethrin inhalation because of the use of mosquito coils and vaporizers, our results for the first time prove that oral exposure to allethrin could affect fertility and may contribute to deregulation of cell cycle in the male reproductive tract. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT The increasing use of products derived from nanotechnology has raised concerns about their potential toxicity, especially at the immunocompetence level in organisms. This study compared the immunotoxicity of cadmium sulfate/cadmium telluride (CdS/Cd-Te) mixture quantum dots (QDs) and their dissolved components, cadmium chloride (CdCl 2 )/sodium telluride (NaTeO 3 ) salts, and a CdCl 2 /NaTeO 3 mixture on four animal models commonly used in risk assessment studies: one bivalve ( Mytilus edulis ), one fish ( Oncorhynchus mykiss ), and two mammals (mice and humans). Our results of viability and phagocytosis biomarkers revealed that QDs were more toxic than dissolved metals for blue mussels. For other species, dissolved metals (Cd, Te, and Cd-Te mixture) were more toxic than the nanoparticles (NPs). The most sensitive species toward QDs, according to innate immune cells, was humans (inhibitory concentration [IC 50 ] = 217 μg/mL). However, for adaptative immunity, lymphoblastic transformation in mice was decreased for small QD concentrations (EC 50 = 4 μg/mL), and was more sensitive than other model species tested. Discriminant function analysis revealed that blue mussel hemocytes were able to discriminate the toxicity of QDs, Cd, Te, and Cd-Te mixture (Partial Wilk's λ = 0.021 and p 〈 0.0001). For rainbow trout and human cells, the immunotoxic effects of QDs were similar to those obtained with the dissolved fraction of Cd and Te mixture. For mice, the toxicity of QDs markedly differed from those observed with Cd, Te, and dissolved Cd-Te mixture. The results also suggest that aquatic species responded more differently than vertebrates to these compounds. The results lead to the recommendation that mussels and mice were most able to discriminate the effects of Cd-based NPs from the effects of dissolved Cd and Te at the immunocompetence level. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Biomarkers are an important tool in laboratory assays that link exposure or effect of specific toxicants to key molecular and cellular events, but they have not been widely used in invertebrate populations exposed to complex mixtures of environmental contaminants in their natural habitats. The present study focused on a battery of biomarkers and their comparative analysis in natural populations of the benthic larvae of Chironomus riparius ( Diptera ) , sampled in three differentially polluted rivers (the Con, Sar, and Louro in Galicia, Spain). In our study, some parameters were identified, such as hsp70 gene activity, GST enzymatic activity, total glycogen content and mouthpart deformities, which showed significant differences among populations from the three rivers that differed in the levels and types of sedimentary contaminants analyzed (metals, organic-chlorine pesticides, alkylphenols, pharmaceutical, and personal care products). In contrast to these sensitive biomarkers, other parameters showed no significant differences ( hsc70 gene, EcR gene, P450 gene, RNA:DNA ratio, total protein content), and were stable even when comparing field and nonexposed laboratory populations. The hsp70 gene seems to be particularly sensitive to conditions of pollutant exposure, while its constitutive counterpart hsc70 showed invariable expression, suggesting that the hsc70 / hsp70 ratio may be a potential indicator of polluted environments. Although further studies are required to understand the correlation between molecular responses and the ecological effects of pollutants on natural populations, the results provide new data about the biological responses to multiple-stressor environments. This field study adds new molecular endpoints, including gene expression, as suitable tools that, complementing other ecotoxicological parameters, may help to improve the methodologies of freshwater monitoring under the increasing burden of xenobiotics. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Alpha-cypermethrin (α-CYP) is one of the most widely used insecticides. It may become an air pollutant and adversely affect the health. The present study was designed to determine whether treatment with N -acetyl cysteine (NAC), a well-known antioxidant, can be useful for the management of the deleterious effects of α-CYP on lung tissues. For this purpose, thirty two male rats were divided into four different groups (eight rats for each). Group (I) gavaged with corn oil (control group), group (II) gavaged daily with NAC (150 mg kg −1 body weight), group (III) gavaged with α-CYP (14.5 mg kg −1 body weight/day, dissolved in corn oil), group (IV) gavaged with NAC then with α-CYP 2 h later for 12 weeks. α-CYP significantly increased serum lactate dehydrogenase (LDH) and pulmonary malondialdehyde (MDA) levels, while decreased the activities of catalase (CAT) and superoxide dismutase (SOD) as well as reduced glutathione (GSH) content in lung. It also provoked higher levels of serum nitric oxide (NO), lung interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), hydroxyproline (Hyp) as well as heme oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF- К B) gene expression in lung tissues. Histopathological alterations in lung with congestion, cellular infiltration, necrotic changes and thickening of inter-alveolar septa were observed following α-CYP administration. NAC reduced the adverse effects of α-CYP on lung tissues and improved the histological architecture of lung since it showed antioxidant, anti-inflammatory and antifibrotic effects on lung tissues. Our results indicate that NAC exerts a potent protective effect against α-CYP-induced oxidative damage and inflammation in lung tissues. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Exposure to diesel engine exhaust particles (DEPs), representing a complex and variable mixture of components, has been linked with cellular production and release of several types of mediators related to pulmonary inflammation. A key challenge is to identify the specific components, which may be responsible for these effects. The aim of this study was to compare the proinflammatory potential of two DEP-samples with contrasting contents of polycyclic aromatic hydrocarbons (PAHs) and metals. The DEP-samples were compared with respect to their ability to induce cytotoxicity, expression and release of proinflammatory mediators (IL-6, IL-8), activation of mitogen-activated protein kinases (MAPKs) and expression of CYP1A1 and heme oxygenase-1 (HO-1) in human bronchial epithelial (BEAS-2B) cells. In addition, dithiothreitol and ascorbic acid assays were performed in order to examine the oxidative potential of the PM samples. The DEP-sample with the highest PAH and lowest metal content was more potent with respect to cytotoxicity and expression and release of proinflammatory mediators, CYP1A1 and HO-1 expression and MAPK activation, than the DEP-sample with lower PAH and higher metal content. The DEP-sample with the highest PAH and lowest metal content also possessed a greater oxidative potential. The present results indicate that the content of organic components may be determinant for the proinflammatory effects of DEP. The findings underscore the importance of considering the chemical composition of particulate matter-emissions, when evaluating the potential health impact and implementation of air pollution regulations. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.