Abstract
The anticoccidial properties of toltrazuril inEimeria falciformis-infected mice were potentiated by the simultaneous application of pyrimethamine, trimethoprim, or sulfadimidine. The same drugs potentiate the effect of toltrazuril by killingE. tenella schizonts in chicken kidney-cell cultures. Activities of some enzymes of the respiratory chain, such as succinate-cytochrome C reductase and NADH oxidase and succinate oxidase from mouse liver, were reduced in the presence of toltrazuril. The same effects could be observed when the activities of NADH oxidase and fumarate reductase from the nematodeAscaris suum were determined in the presence of the drug. Vertebrate enzymes involved in pyrimidine synthesis, e.g., dihydrofolate reductase from chicken liver, were also affected by toltrazuril; however, this effect was 500 times weaker than that shown by pyrimethamine. Toltrazuril also showed an inhibitory effect on the dihydroorotate-cytochrome C reductase from mouse liver. Our results suggest that toltrazuril primarily affects the respiratory chain and secondarily, two enzymes involved in pyrimidine synthesis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Doran DJ (1970)Eimeria tenella: from sporozoites to oocystes in cell culture. Proc Helminthol Soc Wash 37:84–92
Haberkorn A (1986) Use of a mouse coccidiosis model for determining anticoccidial efficacy in poultry. In: McDougald LR, Long PL, Joyner LP (eds) Research in avian coccidiosis. Proceedings of the Georgia Coccidiosis Conference, November 19–21, 1985, Athens, Ga, pp 263–270
Haberkorn A, Schulz HP (1981) Experimental chemotherapy of mammalian coccidiosis with Bay g7183. Zentralbl Bakteriol Parasitenkd Infektionskr Hyg Abt Orig Reihe A 250:260–267
Haberkorn A, Stoltefuss J (1987) Untersuchungen zum Wirkungsspektrum von Toltrazuril, einem neuen Kokzidiose-Mittel. Vet Med Nachr 1:22–32
Hammond DJ, Burchell JR, Pudney M (1985) Inhibition of pyrimidine biosynthesis de novo inPlasmodium falciparum by 2-(4-t-butyl-cyclohexyl)-3-hydroxy-1,4-naphthoquinone in vitro. Mol Biochem Parasitol 14:97–109
Köhler P, Bachmann R (1978) The effects of the antiparasitic drugs levamisole, thiabendazole, praziquantel and chloroquine on the mitochondrial electron transport in muscle tissue fromAscaris suum. Mol Pharmacol 14:155–163
Mehlhorn H, Ortmann-Falkenstein G, Haberkorn A (1984) The effects of sym. triazinones on developmental stages ofEimeria tenella, E. maxima andE. acervulina: a light and electron microscopical study. Z. Parasitenkd 70:173–182
Peters W (1984) Drug combinations. In: Peters W, Richards WHG (eds) Handbook of experimental pharmacology, vol 68II. Springer, Berlin Heidelberg New York Tokyo, pp 225–236
Robinson J, Cooper JM (1970) Method of determining oxygen concentrations in biological media, suitable for calibration of the oxygen electrode. Anal Biochem 33:390–399
Ryley JF, Wilson RG (1976) Drug screening in cell culture for the detection of anticoccidial activity. Parasitology 73:137–148
Wang CC (1982) Biochemistry and physiology of coccidia. In: Long LL (ed) The biology of Coccidia. University Park, Baltimore, pp 167–228
Author information
Authors and Affiliations
Additional information
Dedicated to Prof. Dr. H. Debuch on the occasion of her seventieth birthday
Rights and permissions
About this article
Cite this article
Harder, A., Haberkorn, A. Possible mode of action of toltrazuril: studies on twoEimeria species and mammalian andAscaris suum enzymes. Parasitol Res 76, 8–12 (1989). https://doi.org/10.1007/BF00931064
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00931064