Article ID Journal Published Year Pages File Type
2471333 Veterinary Parasitology 2009 13 Pages PDF
Abstract

A study has been carried out to determine the relative activity of triclabendazole (TCBZ) and its sulphoxide (TCBZSO) and sulphone (TCBZSO2) metabolites against the adult stage of the liver fluke, Fasciola hepatica. Flukes were incubated for 24 h in vitro in 15 μg/ml of each of the compounds and prepared for scanning and transmission electron microscopy.All three compounds induced changes to the surface morphology of the fluke, the changes comprising swelling and blebbing to a greater or lesser extent in different regions of the fluke. TCBZSO2 was more disruptive anteriorly and TCBZSO posteriorly.Internal ultrastructural changes were evident following incubation with each of the compounds, with an order of severity TCBZSO2 > TCBZSO > TCBZ. Swelling of the basal infolds and mitochondria were observed in the tegumental syncytium. In the tegumental cell bodies, there was a reduction in the number of secretory bodies, disruption of the Golgi complexes and swelling of the mitochondria. Severe flooding of the internal tissues was observed with TCBZSO2 and, to a lesser extent, with TCBZSO and TCBZ.The results demonstrate that both TCBZ and TCBZSO2 are capable of disrupting the fluke in vitro and are not the inactive compounds they were assumed to be previously. They may well contribute to drug action in vivo as well, indicating that drug action is due to the additive effects of several metabolites, rather than being due to a single active metabolite, namely, TCBZSO.

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