Effects of feeding 2(3)-tert-butyl 4-hydroxyanisole (BHA) and 3, 5-di-tert-butyl 4-hydroxytoluene (BHT) on the rates of mixed function oxidation and conjugation enzyme reactions have been determined using isolated hepatic microsomal fractions and isolated perfused livers of mice. The treatments with either of the antioxidants have increased the rates of O-demethylation for p-nitroanisole and of O-deethylation for 7-ethoxycoumarin up to 2-fold, both in microsomes and in perfused liver. Analysis of the perfusate showed that the increased amounts of p-nitrophenol and 7-hydroxycoumarin produced by the elevated mixed-function oxidase activities were reflected by the increase in the amounts of glucuronide conjugates and not in the increase for the amounts of the sulfate ester conjugates. Comparison of results also indicated that in the perfused liver, the maximal rate of metabolite conjugation is limited by the maximal rates of the initial mixed function oxidase activities.
Alkylation ; Animal ; Anisoles/metabolism ; Anisoles/pharmacology* ; Butylated Hydroxyanisole/administration & dosage ; Butylated Hydroxyanisole/pharmacology* ; Butylated Hydroxytoluene/administration & dosage ; Butylated Hydroxytoluene/analogs & derivatives* ; Butylated Hydroxytoluene/pharmacology ; Comparative Study ; Coumarins/metabolism ; Female ; Glucuronosyltransferase/metabolism ; Liver/metabolism* ; Mice ; Microsomes, Liver/enzymology ; Microsomes, Liver/metabolism* ; Mixed Function Oxygenases/metabolism ; Oxidation-Reduction ; Perfusion ; Support, U.S. Gov't, P.H.S.