Decrease in hepatic microsomal UDP-glucuronosyl-transferase activity in rats and cattle with fascioliasis: impaired in vitro glucuronidation of oxyclozanide.
The effects of liver fluke infection (Fasciola hepatica) on hepatic microsomal UDP-glucuronosyl-transferase 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 glucuronic 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.
D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy* / Q000201:enzymology; D005210:Fasciola hepatica / Q000302:isolation & purification; D005211:Fascioliasis / Q000188:drug therapy* / Q000201:enzymology / Q000662:veterinary; D005243:Feces / Q000469:parasitology; D005965:Glucuronates / Q000378:metabolism; D020723:Glucuronic Acid; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism; D010097:Oxyclozanide / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012457:Salicylamides / Q000627:therapeutic use*
D005965:Glucuronates; D009596:Nitrophenols; D012457:Salicylamides; D010097:Oxyclozanide; D020723:Glucuronic Acid; D014453:Glucuronosyltransferase; C024836:4-nitrophenol