Abstract
In the present study, the effects of the enantiomers of the anthelmintic drug praziquantel (PZQ) and its main metabolitetrans-4-hydroxypraziquantel (TRANS) on pairs ofSchistosoma mansoni worms were examined in vitro. Highly purified enantiomers (optical purity, >99.9% for PZQ and 99.0% for TRANS) were used. Paired worms were incubated for 4 h in RPMI medium containing 0.01, 0.02, 0.075, 0.1, 2.5, 10, and 100 μg PZQ or TRANS enantiomers/ml, respectively, before being transferred to drug-free medium for another 20 h. PZQ is used as a racementa in the therapy, and its effect is attributed to the R(−)-enantiomer. R(−)-PZQ and R(−)-TRANS proved to be at least 105 times more effective than the respective S(+)enantiomers, causing tegumental damage and surface blebbing onS. mansoni. As judged from the effective doses in 50% of the worms (ED50 values); R(−)-PZQ and R(−)-TRANS showed nearly the same efficacy against adultS. mansoni. Male worms reacted more sensitively than did females. As determined by scanning electron microscopy, alterations in lethally damaged worms depended on the drug used, even following incubation at the lowest concentration tested (0.01 μg/ml). Worms exposed to R(−)-TRANS were elongated, whereas treatment with R(−)-PZQ led to contractions and twisted parasites. Both compounds caused excessive surface blebbing along the dorsal side of the worms' tegument.
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Abbreviations
- B :
-
boss
- CG :
-
canalis gynaecophorus
- F :
-
female
- IT :
-
invagination of the tegument
- M :
-
male
- OS :
-
oral sucker
- SC :
-
sensory cilium
- SP :
-
spine
- V :
-
vacuole
- VS :
-
ventral sucker
References
Andrews P (1981) A summary of the efficacy of praziquantel against schistosomes in animal experiments and notes on its mode of action. Arzneimittelforschung 31:538–541
Andrews P (1985) Praziquantel: mechanisms of anti-schistosomal activity. Pharmacol Ther 29:129–156
Andrews P, Thomas H, Pohlke R, Seubert J (1983) Praziquantel. Med Res Rev 3:147–200
Becker B, Mehlhorn H, Andrews P, Thomas H (1980a) Scanning and transmission electron microscope studies on the efficacy of praziquantel onHymenolepis nana (Cestoda) in vitro. Z Parasitenkd 61:121–133
Becker B, Mehlhorn H, Andrews P, Thomas H, Eckert J (1980b) Light and electron microscopic studies on the effects of praziquantel onSchistosoma mansoni, Dicrocoelium dendriticum, andFasciola hepatica (Trematoda) in vitro. Z Parasitenkd 63:113–128
Blaschke G, Walther B (1985) Konfiguration der Praziquantel-Enantiomere. Chem Ber 4620–4622
Gönnert R, Andrews P (1977) Praziquantel, a new broad-spectrum antischistosomal agent. Z Parasitenkd 52:117–127
Kaup A (1989) Stereoselektive Biotransformation des Praziquantels — Untersuchung von Human- und Rattenseren. Doctoral Thesis. Westfälische Wilhelms-Universität, Münster
Kiec-Kononowicz K, Farghaly ZS, Blaschke G (1990) Synthesis and properties ofcis- andtrans-4-hydroxypraziquantel. Arch Pharm (Weinheim) 324:235–237
Marrinder S, Armour J (1986) Nematode infections of domestic animals: gastrointestinal infections. In: Campbell WC, Rew TS (eds) Chemotherapy of parasitic diseases. Plenum, New York, p 297
Mehlhorn H, Becker B, Andrews P, Thomas H, Frenkel JK (1981) In vivo and in vitro experiments on the effects of praziquantel onSchistosoma mansoni. A light and electron microscopic study. Arzneimittelforschung 31:544–554
Mehlhorn H, Kojima S, Rim HJ, Ruenwongsa P, Andrews P, Thomas H, Bunnag B (1983) Ultrastructural investigations on the effects of praziquantel on human trematodes from Asta:Clonorchis sinensis, Metagonimus yokogawai, Opisthorchis viverrini, Paragonimus westermani andSchistosoma japonicum. Arzneimittelforschung 33:91–98
Patzschke K, Pütter J, Wegener LA, Horster FA, Diekmann HW (1979) Serum concentrations and renal excretion in humans after oral administration of praziquantel—results of three determination methods. Eur J Drug Metab Pharmacokinet 4:149–156
Schmahl G, Mehlhorn H (1985) Treatment of fish parasites: 1. Praziquantel effective against Monogenea (Dactylogyrus vasiator, Dactylogyrus extensus, Diplozoon paradoxum). Z Parasitenkd 71:727–737
Siefker C, Pax RA, Bennett JL (1983)Schistosoma mansoni: a comparison of male and female muscle physiology. Comp Biochem Physiol 76:377–382
Shaw MK, Erasmus DA (1983)Schistosoma mansoni: changes in elemental composition in relation to the age and sexual status of the worms. Parasitology 86:439–453
Shaw MK, Erasmus DA (1984)Schistosoma mansoni: electron probe X-ray microanalysis of the elemental composition of the tegumental and subtegumental tissues of adult worms.Exp Parasitol 58:163–181
Thomas H, Gönnert R (1977) The efficacy of praziquantel against cestodes in animals. Z Parasitenkd 52:117–127
Westhoff F (1991) Stereoselektive Biotransformation des Praziquantels in vivo and in vitro. Doctoral Thesis, Westfälische Wilhelms-Universität, Münster
Xiao SH, Catto BA, Webster LT Jr (1985a) Effects of praziquantel on different developmental stages ofSchistosoma mansoni in vitro and in vitro. J Infect Dis 151:1130–1137
Xiao SH, Guo HF, Dai ZQ, Zhang RQ (1985b) Effect of calcium, magnesium and temperature on praziquantel-induced tegument damage of maleSchistosoma japonicum. Acta Pharmacol Sin 6:59–62
Xiao SH, You JQ, Guo HF, Catto BA (1991) Uptake and effect of praziquantel and the major human oxidative metabolite 4-hydroxypraziquantel bySchistosoma japonicum. J Parasitol 77:241–245
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Staudt, U., Schmahl, G., Blaschke, G. et al. Light and scanning electron microscopy studies on the effects of the enantiomers of praziquantel and its main metabolite onSchistosoma mansoni in vitro. Parasitol Res 78, 392–397 (1992). https://doi.org/10.1007/BF00931694
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DOI: https://doi.org/10.1007/BF00931694