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How anthelmintics help us to understand helminths

Published online by Cambridge University Press:  06 April 2009

H. Vanden Bossche
Affiliation:
Laboratory of Comparative Biochemistry, Research Laboratories, Janssen Pharmaceutica, B-2340 Beerse, Belgium

Extract

Study of the mode of action of the anti-parasitic ‘hydrogenophore’, closantel, revealed that mitochondria isolated from livers of untreated rats, 13 weeks after infection with Fasciola hepatica metacercariae, were uncoupled. This uncoupling of mitochondria might be induced by a product(s) excreted by the liver fluke. The lipid extractable product(s) binds to albumin and has a molecular weight between 500 and 1000 Daltons. A second unexpected finding indicates that closantel affects the motility of Schistosoma mansoni in vitro by interferin with mitochondrial ATP synthesis. The results obtained are suggestive of a role for aerobic metabolism in the generation of energy required for motility.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1985

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References

REFERENCES

Atkinson, D. E., & Walton, G. M., (1967). Adenosine triphosphate conversion in metabolic regulation. Rat liver citrate cleavage enzyme. Journal of Biological Chemistry 242, 3234–44.CrossRefGoogle Scholar
Borgers, M., De Nollin, S., Verheyen, A., De Brabander, M., & Thienpont, D., (1975). Effects of new anthelmintics on the microtubular system of parasites. In Microtubules and Microtubule Inhibitors (ed. Borgers, M. and De Brabander, M.), pp. 497508. Amsterdam: North–Holland.Google Scholar
Bueding, E., (1950). Carbohydrate metabolism of Schistosoma mansoni. Journal of General Physiology 33, 475–95.CrossRefGoogle ScholarPubMed
Chiew, Y. Y., Sullivan, P. A., & Shepherd, M. G., (1982). The effects of ergosterol and alcohols on germ-tube formation and chitin synthase in Candida albicans. Canadian Journal of Biochemistry 60, 1520.CrossRefGoogle ScholarPubMed
Coles, G. C., (1972). Oxidative phosphorylation in adult sSchistosoma mansoni. Nature, London 240, 488–9.CrossRefGoogle ScholarPubMed
Coles, G. C., (1984). Recent advances in schistosome biochemistry. Parasitology 89, 603–37.CrossRefGoogle ScholarPubMed
Del Castillo, J., (1969). Pharmacology of nematoda. In Chemical Zoology (ed. Florkin, M. and Scheer, B. T.), pp. 521–54. New York: Academic Press.CrossRefGoogle Scholar
Duvall, R. H., & Dewitt, W. B., (1967). An Improved Perfusion Technique For Recovering Adult Schistosomes from laboratory animals. The American Journal of Tropical Medicine and Hygiene 16, 483–6.CrossRefGoogle ScholarPubMed
Edwards, D., (1980). Mechanisms of selective toxicity of metronidazole and other nitroimidazole drugs. British Journal of Venereal Diseases 56, 285–90.Google ScholarPubMed
Folch, J., Lees, M., & Sloane-Stanley, G. H., (1957). A simple method for the isolation and purification of total lipids from animal tissues. Journal of Biological Chemistry 226, 497509.CrossRefGoogle ScholarPubMed
Gale, E. F., Cundliffe, E., Reynolds, P. E., Richmond, M. H., & Waring, M. J., (1981). The Molecular Basis of Antibiotic Action. London: John Wiley and Sons.Google Scholar
Gibbons, G. F., Mitbopoulos, K. A., & Myant, N. B., (1982). Biochemistry of Cholesterol. Amsterdam: Elsevier Biomedical Press.Google Scholar
Goodwin, L. G., (1980). New drugs for old diseases. Transactions of the Royal Society of Tropical Medicine and Hygiene 74, 17.CrossRefGoogle ScholarPubMed
Guerrero, J., (1984). Closantel: a review of its antiparasitic activity. Preventive Veterinary Medicine 2, 317–27.CrossRefGoogle Scholar
Kane, H. J., Behm, C. A., & Bryant, C., (1980). Metabolic studies on the new fasciolicidal drug, closantel. Molecular and Biochemical Parasitology 1, 347–55.CrossRefGoogle ScholarPubMed
Paton, W., (1984). Man and Mouse. Animals in Medical Research, p. 22. Oxford: Oxford University Press.Google Scholar
Pax, R., Bennett, J. L., & Fetterer, R., (1978). A benzodiazepine derivative and praziquantel: effects on musculature of Schistosoma mansoni and Schistosoma japonicum. Naunyn Schmiedebergs Archiv of Pharmacology 304, 309–15.CrossRefGoogle ScholarPubMed
Prichard, R. K., Bachmann, R., Hutchinson, G. W., & Köhler, P., (1982). The effect of praziquantel on calcium in Hymenolepis diminuta. Molecular Biochemical Parasitology 5, 297308.CrossRefGoogle ScholarPubMed
Racker, E., (1965). Mechanisms in Bioenergetics. New York: Academic Press.Google Scholar
Sekiya, T., & Nozawa, Y., (1983). Reorganization of membrane ergosterol during cell fission events of Candida albicans: a freeze-fracture study of distribution of filipin-ergosterol complexes. Journal of ultrastructure Research 83, 4857.CrossRefGoogle ScholarPubMed
Schiller, E. L., Bueding, E., Turner, V. M., & Fisher, J., (1975). Aerobic and anaerobic carbohydrate metabolism and egg production of Schistosoma mansoni in vitro. Journal of Parasitology 61, 385–9.CrossRefGoogle ScholarPubMed
Sharpe, M. J., (1980). Changes in the adenylate energy charge of Nematospiroides dubius and Trichostrongylus colubriformis paralysed by levamisole in vitro. Parasitology 81, 593601.CrossRefGoogle Scholar
Travis, J., Bowen, J., Tewksbury, D., Johnson, D., & Pannell, R., (1976). Isolation of albumin from whole human plasma and fractionation of albumin-depleted plasma. The Biochemical Journal 157, 301–6.CrossRefGoogle ScholarPubMed
Vanden Bossche, H., (1985). Biochemical targets for antifungal azole derivatives. Hypothesis on the mode of action. Current Topics in Medical Mycology (in the Press.)CrossRefGoogle ScholarPubMed
Vanden Bossche, H., Lauwers, W., Willemsens, G., Marichal, P., Cornelissen, F., & Cools, W., (1984). Molecular basis for the antimycotic and antibacterial activity of N-substituted imidazoles and triazoles: the inhibition of isoprenoid biosynthesis. Pesticide Sciences 15, 188–98.CrossRefGoogle Scholar
Vanden Bossche, H., Verheyen, A., Verhoeven, H., & Arnouts, D., (1983). Alterations in rat liver mitochondria caused by Fasciola hepatica. In From Parasitic Infection to Parasitic Disease (ed. Gigase, P. L. and Van Marck, E. A. E.), pp. 30–8. Basel: S. Karger.Google Scholar
Vanden Bossche, H., Verhoeven, H., & Lauwers, H., (1980). Uncoupling of liver mitochondria associated with fascioliasis in rats — normalization by closantel. In The Host Invader Interplay (ed. Vanden Bossche, H.), pp. 699704. Amsterdam: Elsevier Biomedical Press.Google Scholar
Vanden Bossche, H., Verhoeven, H., Vanparijs, O., Lauwers, H., & Thienpont, D., (1979). Cosantel, a new antiparasitic hydrogen ionophore. Archives Internationales de Physiologie et de Biochimie 87, 851–2.Google Scholar
Vanden Bossche, H., Willemsens, G., Cools, W., Lauwers, W. F. J., & Le Jeune, L., (1978). Biochemical effects of miconazole on fungi. II. Inhibition of ergosterol biosynthesis in Candida albicans. Chemical–Biological Interactions 21, 5978.CrossRefGoogle Scholar
Vanden Bossche, H., Willemsens, G., Cools, W., Marichal, P., & Lauwers, W., (1983 b). Hypothesis on the molecular basis of the antifungal activity of N-substituted imidazoles and triazoles. Biochemical Society Transactions 11, 665–7.CrossRefGoogle Scholar
Van Noordwijk, J., & De Wolf, J. N., (1963). Effect of pH and calcium concentration on paralytic activity of isopelletierine studied on the liver fluke F. hepatica L. Acta Physiologica et Pharmacologica Neerlandica 12, 3047.Google Scholar
Van Oordt, B. E. P., & Van den Bergh, S. G., (1983). The energy metabolism of the adult Schistosoma mansoni is for a large part aerobic. Abstract S-15-WE-167. 15th FEB8 Meeting(Brussels),Abstract Book, p. 304.Google Scholar
World Health Organization (1984). Report of the scientific working group on the biochemistry and chemotherapy of schistosomiasis. TDR /SCH-SWG (5)/84.1. Geneva: WHO.Google Scholar
Xiao, S.-H., Friedman, P. A., Catto, B. A., & Webster, L. T., (1984). Praziquantel–induced vesicle formation in the tegument of male Schistosoma mansoni is calcium dependent. Journal of Parasitology 70, 177–9.CrossRefGoogle ScholarPubMed