Relative activity of triclabendazole metabolites against the liver fluke, Fasciola hepatica

A study has been carried Out to determine the relative activity Of triclabendazole (TCBZ) and its sulphoxide (TCBZ(center dot)SO) and sulphone (TCBZ(center dot)SO(2)) metabolites against the adult stage of the liver fluke, Fasciola hepatica. Flukes were incubated for 24 h in vitro in 15 mu g/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. TCBZ(center dot)SO(2) was more disruptive anteriorly and TCBZ center dot SO posteriorly. Internal ultrastructural changes were evident following incubation with each of the compounds, with all order of severity TCBZ(center dot)SO(2) > TCBZ(center dot)SO > TCBZ. Swelling of the basal infolds and mitochondria were observed in the tegumental syncytium. in the tegumental cell bodies, there was a reduction on the number of secretory bodies, disruption of the Golgi complexes and swelling of the mitochondria. Severe flooding of the internal tissues was observed with TCBZ(center dot)SO(2) and, to a lesser extent, with TCBZ(center dot)SO and TCBZ. The results demonstrate that both TCBZ and TCBZ(center dot)SO(2) 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, Father than being due to a single active metabolite, namely, TCBZ(center dot)SO. (C) 2008 Elsevier B.V. All rights reserved.