The effect of the sulphoxide metabolite of triclabendazole (‘Fasinex’) on the tegument of mature and immature stages of the liver fluke, Fasciola hepatica | Parasitology | Cambridge Core (original) (raw)

Summary

The effects of the novel benzimidazole, triclabendazole (TCBZ) (‘Fasinex’, Ciba-Geigy), in its active sulphoxide metabolite form (TCBZ-SX), on the tegumental ultrastructure of Fasciola hepatica were determined in vitro by transmission electron microscopy (TEM), using both intact flukes and tissue-slice material. At a concentration of 15 µ/ml, the tegument of the whole adult fluke showed ultrastructural changes only after prolonged time-periods, with vacuolation at the base of the syncytium and accumulation of T2 secretory bodies in the tegumental cells. At a concentration of 50 µ/ml, with both whole flukes and tissue-slices, the tegument appeared extremely abnormal with accumulation of secretory bodies towards the base of the syncytium. With longer incubation times, the tegument was completely sloughed away and the tegumental cells became synthetically inactive. The tegument of the 3-week-old juvenile became progressively convoluted at the apex, while in the basal regions there was severe vacuolation. In the tegumental cells, there were accumulations of T1 secretory bodies. These results confirm TCBZ as a potent fasciolicide, being very effective in disrupting the fluke tegument. They may go some way to explain the mode of action of this important fasciolicide.

References

Allen, R. D. (1987). The microtubule as an intracellular engine. Scientific American 256, 26–33.Google Scholar

Behm, C. A. & Bryant, C. (1979). Anthelmintic action–a metabolic approach (a review). Veterinary Parasitology 5, 39–49.Google Scholar

Bennett, C. E. (1973). An ultrastructural study of the development of Fasciola hepatica L. from the newly excysted juvenile to the adult form in the white mouse. Ph.D. thesis. The Queen's University of Belfast.Google Scholar

Bennett, C. E., Hughes, D. L. & Harness, E. (1980). Fasciola hepatica: changes in tegument during killing of adult flukes surgically transferred to sensitized rats. Parasite Immunology 2, 39–55.Google Scholar

Bennett, C. E. & Threadgold, L. T. (1975). Fasciola hepatica: development of tegument during migration in mouse. Experimental Parasitology 38, 38–55.CrossRefGoogle Scholar

Bennett, J. L. & Köhler, P. (1987). Fasciola hepatica: action in vitro of triclabendazole on immature and adult stages. Experimental Parasitology 63, 49–57.CrossRefGoogle ScholarPubMed

Boray, J. C. (1982). Chemotherapy of fasciolosis. New South Wales Veterinary Proceedings 18, 42–7.Google Scholar

Borgers, M., De Nollin, S., De Brabander, M. & Thienpont, D. (1975 a). Influence of the anthelmintic mebendazole on microtubules and intracellular organelle movement in nematode intestinal cells. American Journal of Veterinary Research 36, 1153–66.Google ScholarPubMed

Borgers, M., De Nollin, S., Verheyen, A., Vanparijs, O. & Thienpont, N. (1975 b). Morphological changes in cysticerci of Taenia taeniaeformis after mebendazole treatment. Journal of Parasitology 61, 830–43.CrossRefGoogle ScholarPubMed

Coles, G. C. (1986). Anthelmintic activity of triclabendazole. Journal of Helminthology 60, 210–12.Google Scholar

De Brabander, M., Geuens, G., Nuydens, R., Willebrords, R., Moeremans, M., Van Ginckel, R., Distelmans, W., Dragonetti, C. & Mareel, M. (1986). Tubulozole: a new stereoselective microtubule inhibitor. Annals of the New York Academy of Sciences 466, 757–66.Google Scholar

Fairweather, I., Anderson, H. R. & Threadgold, L. T. (1986). Fasciola hepatica: tegumental changes induced in vitro by the deacetylated (amine) metabolite of diamphenethide. Experimental Parasitology 62, 336–48.CrossRefGoogle ScholarPubMed

Fairweather, I., Holmes, S. D. & Threadgold, L. T. (1984). Fasciola hepatica: motility responses to fasciolicides in vitro. Experimental Parasitology 57, 209–24.Google Scholar

Fetterer, R. H. (1986). The effect of albendazole and triclabendazole on colchicine binding in the liver fluke Fasciola hepatica. Journal of Veterinary Pharmacology and Therapeutics 9, 49–54.Google Scholar

Geuens, G. M. A., Nuydens, R. M., Willebrords, R. E., Van De Veire, R. M. L., Goosens, F., Dragonetti, C. H., Mareel, M. M. K. & De Brabander, M. J. (1985). Effects of tubulozole on the microtubule system of cells in culture and in vivo. Cancer Research 45, 733–42.Google Scholar

Gorchilova, L., Ŝpaldanová, H. & Polyakova-Krusteva, O. (1988). Morphological characteristics of the tegument and the gut wall of mature Fasciola hepatica after fenbendazole/triclabendazole treatment. Helminthologia 25, 147–55.Google Scholar

Guralp, N. & Tinar, R. (1984). Trematodiasis in Turkey: comparative efficacy of triclabendazole and niclofolan against natural infections of Fasciola hepatica and F. gigantica in sheep. Journal of Helminthology 58, 113–16.CrossRefGoogle Scholar

Hanna, R. E. B. (1976). Fasciola hepatica: a light and electron microscope autoradiographic study of incorporation of monosaccharides into glycogen and glycoprotein. Experimental Parasitology 39, 204–13.Google Scholar

Hanna, R. E. B. (1980 a). Fasciola hepatica: glycocalyx replacement in the juvenile as a possible mechanism for protection against host immunity. Experimental Parasitology 50, 103–14.Google Scholar

Hanna, R. E. B. (1980 b). Fasciola hepatica: an immunofluorescent study of antigenic changes in the tegument during development in the rat and the sheep. Experimental Parasitology 50, 155–70.CrossRefGoogle ScholarPubMed

Hanna, R. E. B. & Threadgold, L. T. (1975). Development of an in vitro technique for cytological investigations of slices of Fasciola hepatica: evaluation by morphological criteria. International Journal for Parasitology 5, 321–31.CrossRefGoogle Scholar

Ibarra, O. F. & Jenkins, D. C. (1984). An in vitro screen for new fasciolicidal agents. Zeitschrift für Parasitenkunde 70, 655–61.CrossRefGoogle Scholar

Iida, H. & Shibata, Y. (1991). Functional Golgi units in microtubule-disrupted cultured atrial monocytes. Journal of Histochemistry and Cytochemistry 39, 1349–55.CrossRefGoogle Scholar

Isseroff, H. & Read, C. P. (1974). Studies on membrane transport–VIII. Absorption of monosaccharides by Fasciola hepatica. Comparative Biochemistry and Physiology [A] 47, 141–52.Google Scholar

Johns, D. R. & Dickeson, S. J. (1979). Efficacy of albendazole against Fasciola hepatica in sheep. Australian Veterinary Journal 55, 431–2.Google Scholar

Kreis, T. E. (1990). Role of microtubules in the organisation of the Golgi apparatus. Cell Motility and the Cytoskeleton 15, 67–70.Google Scholar

Lacey, E. (1988). The role of the cytoskeletal protein, tubulin, in the mode of action and mechanism of drug resistance to benzimidazoles. International Journal for Parasitology 18, 885–936.Google Scholar

Lee, C., Ferguson, M. & Chen, L. B. (1989). Construction of the endoplasmic reticulum. Journal of Cell Biology 109, 2045–55.CrossRefGoogle ScholarPubMed

Lipkowitz, K. B. & McCracken, R. O. (1991). A molecular modeling approach to in vivo efficacy of triclabendazole. Journal of Parasitology 77, 998–1005.Google Scholar

Lubega, G. W. & Prichard, R. K. (1990). Specific interaction of benzimidazole anthelmintics with tubulin: high-affinity binding and benzimidazole resistance in Haemonchus contortus. Molecular Biochemistry and Parasitology 38, 221–32.Google Scholar

Lubega, G. W. & Prichard, R. K. (1991). Interaction of benzimidazole anthelmintics with Haemonchus contortus tubulin: binding affinity and anthelmintic efficacy. Experimental Parasitology 73, 203–13.CrossRefGoogle ScholarPubMed

McCracken, R. O. & Stillwell, W. H. (1991). A possible biochemical mode of action for benzimidazole anthelmintics. International Journal for Parasitology 21, 99–104.Google Scholar

Mareel, M. M. & De Mets, M. (1984). Effect of microtubule inhibitors on invasion and on related activities of tumor cells. International Review of Cytology 90, 125–68.Google Scholar

Rogan, M. T. & Threadgold, L. T. (1984). Fasciola hepatica: tegumental alterations as a consequence of lectin binding. Experimental Parasitology 57, 248–60.Google Scholar

Skuce, P. J. & Fairweather, I. (1989). Fasciola hepatica: the effect of the sodium ionophore monensin on the adult tegument. Parasitology Research 75, 223–32.Google Scholar

Spurr, A. R. (1969). A low-viscosity epoxy resin embedding medium for electron microscopy. Journal of Ultrastructural Research 26, 31–43.Google Scholar

Stitt, A. W. (1991). Studies on the cytoskeleton of Fasciola hepatica and its response to the fasciolicide triclabendazole (‘Fasinex’). Ph.D. thesis, The Queen's University of Belfast.Google Scholar

Stitt, A. W. & Fairweather, I. (1991). Fasciola hepatica: the effect of the microfilament inhibitor cytochalasin B on the ultrastructure of the adult fluke. Parasitology Research 77, 675–85.Google Scholar

Stitt, A. W. & Fairweather, I. (1992). Spermatogenesis in Fasciola hepatica: an ultrastructural comparison of the effects of the anthelmintic, triclabendazole (‘Fasinex’) and the microtubule inhibitor, tubulozole. Invertebrate Reproduction and Development 22, 139–50.Google Scholar

Stitt, A. W. & Fairweather, I. (1993 a). Fasciola hepatica: the effect of the microtubule inhibitors colchicine and tubulozole-C on the ultrastructure of the adult fluke. Parasitology 107, 297–309.Google Scholar

Stitt, A. W. & Fairweather, I. (1993 b). Fasciola hepatica: tegumental surface changes in adult and juvenile flukes following treatment, in vitro, with the sulphoxide metabolite of triclabendazole (‘Fasinex’). Parasitology Research 79, 529–36.Google Scholar

Stitt, A. W., Fairweather, I., Trudgett, A. G. & Johnston, C. F. (1992). Fasciola hepatica: localisation and partial characterization of tubulin. Parasitology Research 78, 103–7.Google Scholar

Terasaki, M., Chen, L. B. & Fujiwara, K. (1986). Microtubules and the endoplasmic reticulum are highly interdependent structures. Journal of Cell Biology 103, 1557–68.Google Scholar

Threadgold, L. T. (1976). Fasciola hepatica: ultrastructure and histochemistry of the glycocalyx of the tegument. Experimental Parasitology 39, 119–34.Google Scholar

Threadgold, L. T. & Brennan, G. p (1978). Fasciola hepatica: basal infolds and associated vacuoles of the tegument. Experimental Parasitology 46, 300–16.Google Scholar

Turner, J. R. & Tartakoff, A. M. (1989). The response of the Golgi complex to microtubule alterations: the roles of metabolic energy and membrane traffic in Golgi complex organization. Journal of Cell Biology 109, 2081–8.Google Scholar

Vale, R. D. (1992). Microtubule motors: many new models off the assembly line. Trends in Biochemical Sciences 17, 300–4.Google Scholar

Van Den Bossche, H., Rochette, F. & Horig, C. (1982). Mebendazole and related anthelmintics. Advances in Pharmacology and Chemotherapy 19, 67–128.Google Scholar

Verheyen, A., Borgers, M., Vanparijs, O. & Thienpont, D. (1976). The effects of mebendazole on the ultrastructure of cestodes. In Biochemistry of Parasites and Host-Parasite Relationships (ed. Van den Bossche, H.), pp. 605–18. Amsterdam: Elsevier/North-Holland Biomedical Press.Google Scholar

Wolff, K., Eckert, J., Schneiter, G. & Lutz, H. (1983). Efficacy of triclabendazole against Fasicola hepatica in sheep and goats. Veterinary Parasitology 13, 145–50.Google Scholar