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Adult triclabendazole-resistant Fasciola hepatica: surface and subsurface tegumental responses to in vitro treatment with the sulphoxide metabolite of the experimental fasciolicide compound alpha

  • M. McCONVILLE (a1), G. P. BRENNAN (a1), M. McCOY (a2), R. CASTILLO (a3), A. HERNANDEZ-CAMPOS (a3), F. IBARRA (a3) and I. FAIRWEATHER (a1)...

Abstract

Mature Fasciola hepatica of the triclabendazole-resistant Sligo isolate were incubated in vitro with 10 μg/ml of the sulphoxide metabolite of compound alpha [5-chloro-2-methylthio-6-(1-naphthyloxy)-H-benzimidazole]; the metabolite will be referred to as alpha.SO. Changes resulting from drug treatment were examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and tubulin immunocytochemistry (ICC). SEM revealed that disruption to the tegumental surface mainly took the form of swelling and blebbing. Extensive spine loss occurred on the ventral surface of the oral cone, and sloughing of the tegument was observed along the lateral margins of the fluke. Examination of sections from the anterior mid-body region at the TEM level revealed that treatment with alpha.SO led to swelling of the basal infolds and mitochondria within the tegumental syncytium; also, accumulations of secretory bodies beneath the apical plasma membrane. The tegumental cell bodies contained swollen mitochondria and cisternae of granular endoplasmic reticulum, but few Golgi complexes were observed. An increase in T2 secretory bodies was observed, whilst in the T1 tegumental cells, the T1 secretory bodies had decreased in number. Immunocytochemical (ICC) studies showed that incubation with alpha.SO, ABZ.SO and TCBZ.SO did not cause significant changes to the distribution of tubulin within the tegumental syncytium of the Sligo isolate. In contrast, alpha.SO, ABZ.SO and TCBZ.SO caused severe disruption to tubulin organization within the syncytial layer of the TCBZ-susceptible Cullompton isolate. The EM results confirm that compound alpha is a fasciolicide capable of disrupting the tegument of mature TCBZ-resistant F. hepatica; however, this was not accompanied by any change in tubulin immunoreactivity.

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Corresponding author

Parasite Proteomics and Therapeutics Research Group, School of Biological Sciences, Queens University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT97BL, Northern Ireland. Tel: +44(0)2890 972298. Fax: +44(0)2890 975877. E-mail: i.fairweather@qub.ac.uk

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REFERENCES

Alvarez, L., Solana, H., Mottier, L., Virkel, G., Fairweather, I. and Lanusse, C. ( 2005). Altered drug influx/efflux and enhanced metabolic activity in triclabendazole-resistant liver flukes. Parasitology 131, 501510.
Anderson, H. R. and Fairweather, I. ( 1995). Fasciola hepatica: ultrastructural changes to the tegument of juvenile flukes following incubation in vitro with the deacetylated (amine) metabolite of diamphenethide. International Journal for Parasitology 25, 319333.
Boray, J. C., Crowfoot, P. D., Strong, M. B., Allison, J. R., Schellenbaum, M., Von Orelli, M. and Sarasin, G. ( 1983). Treatment of immature and mature Fasciola hepatica infections in sheep with triclabendazole. Veterinary Record 113, 315317.
Buchanan, J. F., Fairweather, I., Brennan, G., Trudgett, A. and Hoey, E. M. ( 2003). Fasciola hepatica: surface and internal tegumental changes induced by treatment in vitro with the sulphoxide metabolite of albendazole (‘Valbazen’). Parasitology 126, 141153.
Coles, G. C. and Stafford, K. A. ( 2001). Activity of oxyclozanide, nitroxynil, clorsulon and albendazole against adult triclabendazole-resistant Fasciola hepatica. Veterinary Record 148, 723724.
Coles, G. C., Rhodes, A. C. and Stafford, K. A. ( 2000). Activity of closantel against adult triclabendazole-resistant Fasciola hepatica. Veterinary Record 146, 504.
Fairweather, I. ( 2005). Triclabendazole: new skills to unravel an old(ish) enigma. Journal of Helminthology 79, 227234.
Fairweather, I., Anderson, H. R. and Threadgold, L. T. ( 1986). Fasciola hepatica: tegumental changes induced in vitro by the deacetylated (amine) metabolite of diamphenethide. Experimental Parasitology 62, 336348.
Fairweather, I., Anderson, H. R. and Baldwin, T. M. A. ( 1987). Fasciola hepatica: tegumental surface alterations following treatment in vitro with the deacetylated (amine) metabolite of diamphenethide. Parasitology Research 73, 99106.
Hernández-Campos, A., Ibarra-Velarde, F., Vera-Montenegro, Y., Rivera-Fernández, N. and Castillo, R. ( 2002). Synthesis and fasciolicidal activity of 5-chloro-2-methylthio-6-(1-naphthyloxy)-1 H-benzimidazole. Chemical and Pharmaceutical Bulletin 50, 649652.
Ibarra, F., Vera, Y., Quiroz, H., Cantó, J., Castillo, R., Hernández, A. and Ochoa, P. ( 2004). Determination of the effective dose of an experimental fasciolicide in naturally and experimentally infected cattle. Veterinary Parasitology 120, 6574.
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, 885936.
Mas-Coma, S., Bargues, M. D. and Valero, M. A. ( 2005) Fascioliasis and other plant-borne trematode zoonoses. International Journal for Parasitology 35, 12551278.
McCoy, M. A., Fairweather, I., Brennan, G. P., Kenny, J. M., Ellison, S. and Forbes, A. F. ( 2005). The efficacy of nitroxynil and triclabendazole administered synchronously against juvenile triclabendazole-resistant Fasciola hepatica in sheep. Research in Veterinary Science 78 (Suppl. A), 33.
McKinstry, B., Fairweather, I., Brennan, G. P. and Forbes, A. B. ( 2003). Fasciola hepatica: tegumental surface alterations following treatment in vivo and in vitro with nitroxynil (Trodax). Parasitology Research 91, 251263.
Meaney, M., Fairweather, I., Brennan, G. and Forbes, A. B. ( 2004). Transmission electron microscope study of the ultrastructural changes induced in the tegument and gut of Fasciola hepatica following treatment with clorsulon. Parasitology Research 92, 232241.
Meaney, M., Haughey, S., Brennan, G. P. and Fairweather, I. ( 2005 a). A scanning electron microscope study on the route of entry of clorsulon into the liver fluke, Fasciola hepatica. Parasitology Research 95, 117128and 96, 189198.
Meaney, M., Haughey, S., Brennan, G. P. and Fairweather, I. ( 2005 b). Ultrastructural observations on oral ingestion and trans-tegumental uptake of clorsulon by the liver fluke, Fasciola hepatica. Parasitology Research 95, 201212.
Meaney, M., Fairweather, I., Brennan, G. P., Ramasamy, P. and Subramanian, P. B. ( 2002). Fasciola gigantica: tegumental surface alterations following treatment in vitro with the sulphoxide metabolite of triclabendazole. Parasitology Research 88, 315325.
Meaney, M., Fairweather, I., Brennan, G. P., McDowell, L. S. L. and Forbes, A. B. ( 2003). Fasciola hepatica: effects of the fasciolicide clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes. Parasitology Research 91, 238250.
Moll, L., Gaasenbeek, C. P. H., Vellema, P. and Borgsteede, F. H. M. ( 2000). Resistance of Fasciola hepatica against triclabendazole in cattle and sheep in the Netherlands. Veterinary Parasitology 91, 153158.
Overend, D. J. and Bowen, F. L. ( 1995). Resistance of Fasciola hepatica to triclabendazole. Australian Veterinary Journal 72, 275276.
Rivera, N., Ibarra, F., Zepeda, A., Fortoul, T., Cantó, G., Hernández, A. and Castillo, R. ( 2005). The effect of the 5-chloro-2-methylthio-6-(1-naphtyloxy)-H-benzimidazole on the tegument of immature Fasciola hepatica in their natural host. Parasitology Research 95, 379383.
Rivera, N., Ibarra, F., Zepeda, A., Fortoul, T., Hernández, A., Castillo, R. and Cantó, G. ( 2004). Tegumental surface changes in adult Fasciola hepatica following treatment in vitro and in vivo with an experimental fasciolicide. Parasitology Research 93, 283286.
Rivero, L. M., Jung, H., Castillo, R. and Hernández Campos, A. ( 1998). High-performance liquid chromatographic assay for a new fasciolicide agent, α-BIOF10, in biological fluids. Journal of Chromatography B 712, 237241.
Robinson, M. W., Trudgett, A., Hoey, E. M. and Fairweather, I. ( 2002). Triclabendazole-resistant Fasciola hepatica: β-tubulin and response to in vitro treatment with triclabendazole. Parasitology 124, 325338.
Robinson, M. W., Trudgett, A., Hoey, E. M. and Fairweather, I. ( 2003). The effect of the microtubule inhibitor tubulozole-C on the tegument of triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica. Parasitology Research 91, 117129.
Robinson, M. W., Lawson, J., Trudgett, A., Hoey, E. M. and Fairweather, I. ( 2004). The comparative metabolism of triclabendazole sulphoxide by triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica. Parasitology Research 92, 205210.
Rogan, M. T. and Threadgold, L. T. ( 1984). Fasciola hepatica: tegumental changes as a result of lectin binding. Experimental Parasitology 57, 248260.
Skuce, P. J. and Fairweather, I. ( 1990). The effect of the hydrogen ionophore closantel upon the pharmacology and ultrastrucure of the adult liver fluke Fasciola hepatica. Parasitology Research 76, 241250.
Skuce, P. J., Anderson, H. R. and Fairweather, I. ( 1987). The interaction between the deacetylated (amine) metabolite of diamphenethide (DAMD) and cytochemically demonstrable Na+/K+-ATPase activity in the tegument of Fasciola hepatica. Parasitology Research 74, 161167.
Smeal, M. G. and Hall, C. A. ( 1983). The activity of triclabendazole against immature and adult Fasciola hepatica infections in sheep. Australian Veterinary Journal 60, 329331.
Stitt, A. W. and Fairweather, I. ( 1993 a). Fasciola hepatica: tegumental surface changes in adult and juvenile flukes following treatment in vitro with the sulphoxide metabolite of triclabendazole (Fasinex). Parasitology Research 79, 529536.
Stitt, A. W. and Fairweather, I. ( 1993 b). Fasciola hepatica: the effect of the microtubule inhibitors colchicine and tubulozole-C on the ultrastructure of the adult fluke. Parasitology 107, 297309.
Stitt, A. W. and Fairweather, I. ( 1994). The effect of the sulphoxide metabolite of triclabendazole (‘Fasinex’) on the tegument of mature and immature stages of the liver fluke, Fasciola hepatica. Parasitology 108, 555567.
Turner, K., Armour, J. and Richards, R. J. ( 1984). Anthelmintic efficacy of triclabendazole against Fasciola hepatica in sheep. Veterinary Record 114, 4142.
Vera Montenegro, Y., Ibarra Velarde, F., Liébano Hernández, E., Quiroz Romero, H., Castillo Bocanegra, R., Hernández Campos, A. and Ochoa Galván, P. ( 2004). Efficacy of an experimental fasciolicide against immature and mature Fasciola hepatica in artificially infected calves. Parasitology Research 92, 211214.
Walker, S. M., Mckinstry, B., Boray, J. C., Brennan, G. P., Trudgett, A., Hoey, E. M., Fletcher, H. and Fairweather, I. ( 2004). Response of two isolates of Fasciola hepatica to treatment with triclabendazole in vivo and in vitro. Parasitology Research 94, 427438.
Wolstenholme, A. J., Fairweather, I., Prichard, R., von Samson-Himmelstjerna, G. and Sangster, N. C. ( 2004). Drug resistance in veterinary helminths. Trends in Parasitology 20, 469476.

Keywords

Adult triclabendazole-resistant Fasciola hepatica: surface and subsurface tegumental responses to in vitro treatment with the sulphoxide metabolite of the experimental fasciolicide compound alpha

  • M. McCONVILLE (a1), G. P. BRENNAN (a1), M. McCOY (a2), R. CASTILLO (a3), A. HERNANDEZ-CAMPOS (a3), F. IBARRA (a3) and I. FAIRWEATHER (a1)...

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