HEPATIC-METABOLISM OF SKATOLE IN PIGS BY CYTOCHROME P4502E1

High concentrations of skatole in fat are a major cause of boar taint in intact male pigs. Skatole is metabolized in the liver, and this met abolism could affect concentrations of skatole in fat. In this study, we evaluated the involvement of cytochrome P450, in particular cytochr ome P4502E1, in skatole metabolism in pig liver. Liver microsomes from F-4 European Wild Pig x Swedish Yorkshire intact male pigs were incub ated in a buffer containing NADPH, NADH, and skatole. Several skatole metabolites were detected by HPLC, including 6-hydroxyskatole (pro-MII ), 3-hydroxy-3-methyloxyindole (MIII), and five others not identified in this study. Inhibitors of P450 were added to microsomal incubations , and their effect on the formation of skatole metabolites and skatole disappearance was evaluated. The general cytochrome P450 inhibitors S KF 525A, at a concentration of .2 mM and metyrapone, at a concentratio n of .1 mM decreased the formation of pro-MII (P = .001) to 38.2 and 1 1.6%, respectively, of that of controls. The SKF 525A also reduced the synthesis of MIII and three other metabolites, whereas metyrapone onl y. reduced the disappearance of skatole and synthesis of pro-MII, Inhi bitors specific for cytochrome P4502E1 were more effective in reducing the formation of skatole metabolites than SKF 525A and metyrapone. Ch lorzoxazone and diallyl sulfide reduced (P = .001) the synthesis of pr o-MII to 9.7 and 30.9% of the control rate. The formation of most of t he other skatole metabolites and disappearance of skatole were also re duced with these inhibitors. These results indicate that skatole is me tabolized in pig liver to pro-MII and other metabolites by cytochrome P4502E1.