Isothermal microcalorimetry to study the activity of triclabendazole and its metabolites on juvenile and adult Fasciola hepatica

Isothermal microcalorimetry (IMC) is an analytical tool that continuously measures the heat flow generated by chemical, physical or biological processes. We have demonstrated that IMC is a useful tool to analyze drug effects on helminths, including adult Fasciola hepatica. Here, we used IMC to examine the activity of triclabendazole and its metabolites triclabendazole sulphone and triclabendazole sulphoxide on juvenile and adult F. hepatica. Worms (1 adult or 2-3 juveniles) were placed in 4 or 20 ml glass ampoules containing RPMI 1640 and the test compound (25-100 ?g/ml) and the heat flow and motility of worms was examined with TAM48 and TAMIII isothermal microcalorimetry instruments. IMC was found to be preciselydocument drug effects on juvenile F. hepatica and confirmed the pronounced effect of the benzimidazole derivatives on the motor activity of F. hepatica. Juvenile F. hepatica incubated with100 ?g/ml triclabendazole, triclabendazole sulphone and triclabendazole sulphoxide showed no movements 8.3, 35 and 6 hours post-incubation (all p0.05) and 88 (p<0.05) hours. In conclusion, IMC is useful to document drug effects on juvenile F. hepatica and since rapid technological developments in this field are occurring IMC might also hold promise to study adult F. hepatica in the near future.