DECREASE IN HEPATIC-MICROSOMAL UDP-GLUCURONOSYL-TRANSFERASE ACTIVITY IN RATS AND CATTLE WITH FASCIOLIASIS - IMPAIRED INVITRO GLUCURONIDATION OF OXYCLOZANIDE

The effects of liver fluke infection (Fasciola hepatica) on hepatic microsomal UDP-glucuronosyltransferase activity have been studied in microsomes from experimentally infected rats and naturally infected cattle to see if they explain the toxic episodes observed in parasite-infected animals subjected to intensive chemotherapy with the flukicidal drug oxyclozanide. Dramatic decreases in the activity of this enzyme system with the typical substrate p-nitrophenol were observed in both animal species, even when little or no degenerative lesions could be seen in the liver parenchyma. In vitro there was a similar loss of glueuronic acid conjugation of oxyclozanide by hepatic microsomes from infected cattle. In vivo this would result in slower elimination of the drug and in drug accumulation.