Hepatic cytochrome P450 and flavin cointaining monoogygenase metabolic activities in male and female sheep

Abstract

Xenobiotic metabolizing enzymes play a major role in determining the persistence of therapeutically used drugs in target tissues. Phase 1 oxidative reactions are catalyzed by the cytochrome P450 (CYP) superfamily and the flavin-containing monooxygenase (FMO) system, the most important membranebound mixed function oxidases in mammals. The objective of this work was to evaluate CYP- and FMO-dependent activities in liver microsomes obtained from male and female Romney Marsh sheep aged 8-10 months. The involvement of both enzyme systems on the hepatic enantioselective sulphoxidation of the benzimidazole anthelmintic albendazole (ABZ) was also characterized. CYP- and FMO-dependent metabolic activities were measured by using known marker substrates. The total CYP contents in the hepatic microsomes were 0.51±0.18 (males) and 0.53±0.08 (females) nmol/mg of microsomal protein. No gender differences were observed in CYP1A-, CYP2B-, CYP2C-, CYP3A- and FMO-dependent activities. The metabolic ratios FMO/CYP for the total sulphoxidation of ABZ were 3.35 and 3.58 in male and female sheep, respectively. This finding also indicates no gender differences on the contribution of both enzyme systems to the hepatic metabolism of this anthelmintic. Overall, male and female Romney Marsh sheep displayed similar phase 1 metabolic activities in the liver.