Abstract
The bioconcentration potential of fluoxetine (FLX) and its biological effects were investigated in juvenile Pacific oyster exposed for 28 days to environmentally relevant concentrations of FLX (1 ng L−1, 100 ng L−1 and up to 10 μg L−1). FLX bioaccumulated in oyster flesh resulting in 28-day bioconcentration factors greater than 2,000 and 10,000 by referring to wet and dry weights, respectively. Nevertheless, FLX did not induce oyster mortality, delayed gametogenesis, or lead to adverse histopathological alterations. At the two highest concentrations, despite non-optimal trophic conditions, FLX stimulated shell growth but only in a transient manner, suggesting a role of serotonin in the regulation of feeding and metabolism in bivalves. Those high concentrations seemed to drive bell-shaped responses of catalase and glutathione S-transferase activities throughout the exposure period, which may indicate the activation of antioxidant enzyme synthesis and then an enhanced catabolic rate or direct inhibition of those enzymes. However, no clear oxidative stress was detected because no strong differences in thiobarbituric acid-reactive substance (TBARS) content (i.e. lipid peroxidation) were observed between oyster groups, suggesting that cellular defence mechanisms were effective. These results demonstrate the importance of considering additional biomarkers of oxidative stress to obtain a comprehensive overview of the FLX-induced changes in marine bivalves exposed under realistic conditions. Considering the battery of biomarkers used, FLX appears to induce little or no effects on oyster physiology even at a concentration of 10 μg L−1. These results do not confirm the lowest observed effect concentration (LOEC) values reported by some authors in other mollusc species.
Similar content being viewed by others
References
Aiello EL (1970) Nervous and chemical stimulation of gill cilia in bivalve molluscs. Physiol Zool 43:60–70
Altamura AC, Moro AR, Percudani M (1994) Clinical pharmacokinetics of fluoxetine. Clin Pharmacokinet 26(3):201–214
Amachree D, Moody AJ, Handy RD (2013) Comparison of intermittent and continuous exposures to cadmium in the blue mussel, Mytilus edulis: accumulation and sub-lethal physiological effects. Ecotoxicol Environ Saf 95:19–26
Ansaldo M, Sacristán H, Wider E (2007) Does starvation influence the antioxidant status of the digestive gland of Nacella concinna in experimental conditions? Comp Biochem Physiol C Toxicol Pharmacol 146(1–2):118–123
Au DW (2004) The application of histo-cytopathological biomarkers in marine pollution monitoring: a review. Mar Pollut Bull 48(9–10):817–834
Benotti MJ, Brownawell BJ (2007) Distributions of pharmaceuticals in an urban estuary during both dry- and wet-weather conditions. Environ Sci Technol 41(16):5795–5802
Blair BD, Crago JP, Hedman CJ, Klaper RD (2013) Pharmaceuticals and personal care products found in the Great Lakes above concentrations of environmental concern. Chemosphere 93(9):2116–2123
Bradford M (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye blinding. Anal Biochem 72:248–254
Bringolf RB, Heltsley RM, Newton TJ, Eads CB, Fraley SJ, Shea D, Cope WG (2010) Environmental occurrence and reproductive effects of the pharmaceutical fluoxetine in native freshwater mussels. Environ Toxicol Chem 29(6):1311–1318
Brooks BW, Foran CM, Richards SM, Weston J, Turner PK, Stanley JK, Solomon KR, Slattery M, La Point TW (2003) Aquatic ecotoxicology of fluoxetine. Toxicol Lett 142(3):169–183
Buisson S, Bouchart V, Guerlet E, Malas JP, Costil K (2008) Level of contamination and impact of pesticides in cupped oyster, Crassostrea gigas, reared in a shellfish production area in Normandy (France). J Environ Sci Health B 43:655–664
Burgess JG, Iwamoto K, Miura Y, Takano H, Matsunaga T (1993) An optical fibre photobioreactor for enhanced production of the marine unicellular alga Isochrysis aff. galbana T-Iso (UTEX LB 2307) rich in docosahexaenoic acid. Appl Microbiol Biotechnol 39(4–5):456–459
Cachot J, Geffard O, Augagneur S, Lacroix S, Le Menach K, Peluhet L, Couteau J, Denier X, Devier MH, Pottier D, Budzinski H (2006) Evidence of genotoxicity related to high PAH content of sediments in the upper part of the Seine estuary (Normandy, France). Aquat Toxicol 79(3):257–267
Campos B, Garcia-Reyero N, Rivetti C, Escalon L, Habib T, Tauler R, Tsakovski S, Piña B, Barata C (2013) Identification of metabolic pathways in Daphnia magna explaining hormetic effects of selective serotonin reuptake inhibitors and 4-nonylphenol using transcriptomic and phenotypic responses. Environ Sci Technol 47(16):9434–9443
Canesi L, Lorusso LC, Ciacci C, Betti M, Regoli F, Poiana G, Gallo G, Marcomini A (2007) Effects of blood lipid lowering pharmaceuticals (bezafibrate and gemfibrozil) on immune and digestive gland functions of the bivalve mollusc, Mytilus galloprovincialis. Chemosphere 69(6):994–1002
Catterson ML, Preskorn SH (1996) Pharmacokinetics of selective serotonin reuptake inhibitors: clinical relevance. Pharmacol Toxicol 78:203–208
Chatterjee S, Bhattacharya S (1984) Detoxication of industrial pollutants by the glutathione glutathione-S-transferase system in the liver of Anabas testudineus (Bloch). Toxicol Lett 22(2):187–198
Chen M, Ohman K, Metcalfe C, Ikonomou MG, Amatya P, Wilson J (2006) Pharmaceuticals and endocrine disruptors in wastewater treatment effluents and in the water supply system of Calgary, Alberta, Canada. Wat Qual Res J Can 41(4):351–364
Clairbone A (1985) Catalase activity. In: Greenwald RA (ed) Handbook of methods for oxygen radical research. CRC Press, Boca Raton, Florida, pp 283–284
Costil K, Royer J, Ropert M, Soletchnik P, Mathieu M (2005) Spatio-temporal variations in biological performances and summer mortality of the Pacific oyster Crassostrea gigas in Normandy (France). Helg Mar Res 59(4):286–300
Damiens G, His E, Gnassia-Barelli M, Quiniou F, Roméo M (2004) Evaluation of biomarkers in oyster larvae in natural and polluted conditions. Comp Biochem Physiol C Toxicol Pharmacol 138(2):121–128
Daniel WA, Wójcikowski J (1997) Contribution of lysosomal trapping to the total tissue uptake of psychotropic drugs. Pharmacol Toxicol 80:62–68
De los Ríos A, Perez L, Ortiz-Zarragoitia M, Serrano T, Barbero MC, Echavarri-Erasun B, Juanes JA, Orbea A, Cajaraville MP (2013) Assessing the effects of treated and untreated urban discharges to estuarine and coastal waters applying selected biomarkers on caged mussels. Mar Pollut Bull 77(1–2):251–265
Di Poi C, Darmaillacq AS, Dickel L, Boulouard M, Bellanger C (2013a) Effects of perinatal exposure to waterborne fluoxetine on memory processing in the cuttlefish Sepia officinalis. Aquat Toxicol 132–133:84–91
Di Poi C, Evariste L, Serpentini A, Halm-Lemeille MP, Lebel JM, Costil K (2013b) Toxicity of five antidepressant drugs on embryo-larval development and metamorphosis success in the Pacific oyster. Crassostrea gigas Environ Sci Pollut Res. doi:10.1007/s11356-013-2211-y
Di Poi C, Bidel F, Dickel L, Bellanger C (2014) Cryptic and biochemical responses of young cuttlefish Sepia officinalis exposed to environmentally relevant concentrations of fluoxetine. Aquat Toxicol 151:36–54
FAO (2014) http://www.fao.org/fishery/species/3514/en. Accessed 9 June 2014.
Fick J, Lindberg RH, Tysklind M, Larsson DG (2010) Predicted critical environmental concentrations for 500 pharmaceuticals. Regul Toxicol Pharmacol 58(3):516–523
Fong PP (1998) Zebra mussel spawning is induced in locv con- centrations of putative serotonin reuptake inhibitors. Biol Bull 194:143–149
Fong PP, Ford AT (2014) The biological effects of antidepressants on the molluscs and crustaceans: a review. Aquat Toxixol doi:. doi:10.1016/j.aquatox.2013.12.003
Fong PP, Hoy CM (2012) Antidepressants (venlafaxine and citalopram) cause foot detachment from the substrate in freshwater snails at environmentally relevant concentrations. Mar Freshwat Behav Physiol 45:145–153
Franzellitti S, Buratti S, Capolupo M, Du B, Haddad SP, Chambliss CK, Brooks BW, Fabbri E (2013) An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels. Aquat Toxicol 151:14–26
Funes V, Alhama J, Navas JI, López-Barea J, Peinado J (2006) Ecotoxicological effects of metal pollution in two mollusc species from the Spanish South Atlantic littoral. Environ Pollut 139(2):214–223
Gabe M (1968) Techniques histologiques. Masson and Compagnie, Paris, France, 1113 p
Gonzalez-Rey M, Bebianno MJ (2012) Does non-steroidal anti-inflammatory (NSAID) ibuprofen induce antioxidant stress and endocrine disruption in mussel Mytilus galloprovincialis? Environ Toxicol Pharmacol 33:361–371
Gonzalez-Rey M, Bebianno MJ (2013) Does selective serotonin reuptake inhibitor (SSRI) fluoxetine affects mussel Mytilus galloprovincialis? Environ Pollut 173:200–209
Gonzalez-Rey M, Mattos JJ, Piazza CE, Bainy ACD, Bebianno MJ (2014) Effects of active pharmaceutical ingredients mixtures in mussel Mytilus galloprovincialis. Aquat Toxicol doi:. doi:10.1016/j.aquatox.2014.02.006
Gust M, Buronfosse T, Giamberini L, Ramil M, Mons R, Garric J (2009) Effects of fluoxetine on the reproduction of two prosobranch mollusks: Potamopyrgus antipodarum and Valvata piscinalis. Environ Pollut 157(2):423–429
Habig WH, Pabst MJ, Jakobi WB (1974) Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139
Helm MM, Bourne N (2006) Ecloserie de bivalves; un manuel pratique. Lovatelli A (ed) Organisation des Nations Unies pour l’Alimentation et l’Agriculture, Rome, Italie, 184 p
Hiemke C, Härtter S (2000) Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol Ther 85(1):11–28
Honkoop PJC, Luttikhuizen PC, Piersma T (1999) Experimentally extending the spawning season of a marine bivalve using temperature change and fluoxetine as synergistic triggers. Mar Ecol Prog Ser 180:297–300
Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT (2002) Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999–2000: a national reconnaissance. Environ Sci Technol 36:1202–1211
Koutsogiannaki S, Franzellitti S, Fabbri E, Kaloyianni M (2014) Oxidative stress parameters induced by exposure to either cadmium or 17β-estradiol on Mytilus galloprovincialis hemocytes. The role of signaling molecules. Aquat Toxicol 146:186–195
Kwon JW, Armbrust KL (2006) Laboratory persistence and fate of fluoxetine in aquatic environments. Environ Toxicol Chem 25(10):2561–2568
Lazzara R, Blázquez M, Porte C, Barata C (2012) Low environmental levels of fluoxetine induce spawning and changes in endogenous estradiol levels in the zebra mussel Dreissena polymorpha. Aquat Toxicol 106–107:123–130
Lushchak VI, Semchyshyn HM, Lushchak OV (2012) The classic methods to measure oxidative damage: lipid peroxides, thiobarbituric-acid reactive substances, and protein carbonyls. In: Abele D, Vazquez-Medina JP, Zenteno-Savin T (eds) Oxidative stress in aquatic ecosystems. Wiley-Blackwell, Chichester, UK, pp 420–431
Martin-Diaz L, Franzellitti S, Buratti S, Valbonesi P, Capuzzo A, Fabbri E (2009) Effects of environmental concentrations of the antiepilectic drug carbamazepine on biomarkers and cAMP-mediated cell signaling in the mussel Mytilus galloprovincialis. Aquat Toxicol 94(3):177–185
Meredith-Williams M, Carter LJ, Fussell R, Raffaelli D, Ashauer R, Boxall ABA (2012) Uptake and depuration of pharmaceuticals in aquatic invertebrates. Environ Poll 165:250–258
Morton BS (1977) The tidal rhythm of feeding and digestion in the pacific oyster, Crassostrea gigas (Thunberg). J Exp Mar Biol Ecol 26(2):135–151
Mottier A, Kientz-Bouchart V, Serpentini A, Lebel JM, Jha AN, Costil K (2013) Effects of glyphosate-based herbicides on embryo-larval development and metamorphosis in the Pacific oyster, Crassostrea gigas. Aquat Toxicol 128–129:67–78
Nakamura Y, Yamamoto H, Sekizawa J, Kondo T, Hirai N, Tatarazako N (2008) The effects of pH on fluoxetine in Japanese medaka (Oryzias latipes): acute toxicity in fish larvae and bioaccumulation in juvenile fish. Chemosphere 70(5):865–873
Nasci C, Da Ros L, Campesan G, Van Vleet ES, Salizzato M, Sperni L, Pavoni B (1999) Clam transplantation and stress related biomarkers as useful tools for assessing water quality in coastal environments. Mar Pollut Bull 39:255–260
Nentwig G (2007) Effects of pharmaceuticals on aquatic invertebrates. Part II: the antidepressant drug fluoxetine. Arch Environ Contam Toxicol 52:163–170
Nicholson S, Lam PKS (2005) Pollution monitoring in Southeast Asia using biomarkers in the mytilid mussel Perna viridis (Mytilidae: Bivalvia): review article. Environ Int 31:121–132
Oakes KD, Coors A, Escher BI, Fenner K, Garric J, Gust M, Knacker T, Küster A, Kussatz C, Metcalfe CD, Monteiro S, Moon TW, Mennigen JA, Parrott J, Péry AR, Ramil M, Roennefahrt I, Tarazona JV, Sánchez-Argüello P, Ternes TA, Trudeau VL, Boucard T, Van Der Kraak GJ, Servos MR (2010) Environmental risk assessment for the serotonin re-uptake inhibitor fluoxetine: case study using the European risk assessment framework. Integr Environ Assess Manag 6(S1):524–539
Parolini M, Binelli A, Cogni D, Provini A (2010) Multi-biomarker approach for the evaluation of the cyto-genotoxicity of paracetamol on the zebra mussel (Dreissena polymorpha). Chemosphere 79(5):489–498
Paterson G, Metcalfe CD (2008) Uptake and depuration of the anti-depressant fluoxetine by the Japanese medaka (Oryzias latipes). Chemosphere 74(1):125–130
Péry AR, Gust M, Vollat B, Mons R, Ramil M, Fink G, Ternes T, Garric J (2008) Fluoxetine effects assessment on the life cycle of aquatic invertebrates. Chemosphere 73(3):300–304
Saimi Y, Murakami A, Takahashi K (1983) Electrophysiological correlates of nervous control of ciliary arrest response in the gill epithelial cells of Mytilus. Comp Biochem Physiol Part A: Physiol 74(3):499–506
Sánchez-Argüello P, Fernández C, Tarazona JV (2009) Assessing the effects of fluoxetine on Physa acuta (Gastropoda, Pulmonata) and Chironomus riparius (Insecta, Diptera) using a two-species water-sediment test. Sci Total Environ 407(6):1937–1946
Schultz MM, Furlong ET (2008) Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC/ESI/MS/MS. Anal Chem 80(5):1756–1762
Togola A, Budzinski H (2008) Multi-residue analysis of pharmaceutical compounds in aqueous samples. J Chromatogr A 1177:150–158
Vasskog T, Bergersen O, Anderssen T, Jensen E, Eggen T (2009) Depletion of selective serotonin reuptake inhibitors during sewage sludge composting. Waste Manag 29:2808–2815
Viarengo A, Lowe D, Bolognesi C, Fabbri E, Koehler A (2007) The use of biomarkers in biomonitoring: a 2-tier approach assessing the level of pollutant-induced stress syndrome in sentinel organisms. Comp Biochem Physiol C Toxicol Pharmacol 146(3):281–300
Weston J, Huggett D, Allgood J, Foran C, Slattery M (2001) Determination of fluoxetine (Prozac) and norfluoxetine in the aquatic environment. Annual Meeting of the Society of Environmental Toxicology and Chemistry. Baltimore, Maryland
Winstead JT (1995) Digestive tubule atrophy in Eastern oyster, Crassostrea virginica (Gmelin, 1971) exposed to salinity and starvation stress. J Shellfish Res 14:105–111
Acknowledgments
We gratefully acknowledge the staff of the laboratory UMR BOREA at the University of Caen and especially Béatrice Adeline. We are also grateful to our colleagues involved in the French program “Pharm@ecotox” and especially to Dr. Marie Pierre Halm-Lemeille who coordinates the program, for fruitful discussions. We thank Dr. Aude Jouaux, who quantified viral loads in oysters at the “Centre de Référence sur l’Huître” (CRH). We also thank the SATMAR team, who kindly provided us with juvenile oysters and the “Centre de Recherche en Environnement Côtier” (CREC) in Luc-sur-Mer, which provided technical facilities. This study was supported by the French National Research Agency (http://www.agence-nationale-recherche.fr/en/). Finally, we would like to thank the anonymous reviewers for their constructive comments for improving the manuscript.
Author information
Authors and Affiliations
Corresponding author
Additional information
Responsible editor: Cinta Porte
Rights and permissions
About this article
Cite this article
Di Poi, C., Evariste, L., Séguin, A. et al. Sub-chronic exposure to fluoxetine in juvenile oysters (Crassostrea gigas): uptake and biological effects. Environ Sci Pollut Res 23, 5002–5018 (2016). https://doi.org/10.1007/s11356-014-3702-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-014-3702-1