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

Abstract

A study has been carried out to determine the relative activity of triclabendazole (TCBZ) and its sulphoxide (TCBZ SO) and sulphone (TCBZ SO 2) 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. TCBZ SO 2 was more disruptive anteriorly and TCBZ SO posteriorly. Internal ultrastructural changes were evident following incubation with each of the compounds, with an order of severity TCBZ SO 2 > TCBZ SO > 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 TCBZ SO 2 and, to a lesser extent, with TCBZ SO and TCBZ. The results demonstrate that both TCBZ and TCBZ 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, rather than being due to a single active metabolite, namely, TCBZ SO.