The effect of albendazole and triclabendazole on colchicine binding in the liver fluke Fasciola hepatica

Albendazole (ABZ) and its sulfoxide (SX) and sulfone (SO) metabolites inhibit the binding of 3H-colchicine, a ligand with high affinity for tubulin to homogenate preparations of the liver fluke Fasciola hepatica. The relative potency of these compounds is SX greater than ABZ greater than SO. The benzimidazoles (cambendazole, parbendazole, oxibendazole and mebendazole), when tested at a concentration of 10 microM, also inhibited colchicine binding to fluke homogenates. However, a potent new benzimidazole flukacide, triclabendazole (TCB), was without effect on colchicine binding to F. hepatica homogenates. When intact flukes were exposed in vitro to 10(-5)M SX for as little as 5 min the subsequent binding of 3H-colchicine to fluke homogenates was significantly reduced. However, flukes recovered from sheep either 12 or 24 h after treatment with ABZ did not have a decreased ability to bind colchicine, although the non-specific binding was higher in flukes from treated sheep, suggesting some interaction of drug with tubulin in vivo. ABZ, SX and SO were effective in preventing embryonation of fluke eggs at doses as low as 0.01 microM, but TCB was without effect at concentrations as high as 10 microM. The results suggest that ABZ exerts at least part of its anthelmintic effect by interaction with fluke tubulin.