Decrease in hepatic microsomal UDP-glucuronosyl-transferase activity in rats and cattle with fascioliasis: impaired in vitro glucuronidation of oxyclozanide.

Abstract

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.

• Authors: R Maffei Facino, M Carini, C Genchi
• Journal: Toxicology letters (Toxicol Lett) Vol. 26 Issue 1 Pg. 65-71 (Jul 1985) ISSN: 0378-4274 [Print] Netherlands
• PMID: 3927525 (Publication Type: Journal Article)

Chemical References

• Glucuronates
• Nitrophenols
• Salicylamides
• Oxyclozanide
• Glucuronic Acid
• Glucuronosyltransferase
• 4-nitrophenol

Topics

• Animals
• Cattle
• Cattle Diseases (drug therapy, enzymology)
• Fasciola hepatica (isolation & purification)
• Fascioliasis (drug therapy, enzymology, veterinary)
• Feces (parasitology)
• Glucuronates (metabolism)
• Glucuronic Acid
• Glucuronosyltransferase (metabolism)
• Kinetics
• Male
• Microsomes, Liver (drug effects, enzymology, metabolism)
• Nitrophenols (metabolism)
• Oxyclozanide (metabolism, therapeutic use)
• Rats
• Rats, Inbred Strains
• Salicylamides (therapeutic use)