Effect of Antioxidants on Microsomal Enzymes of Rat Liver

Abstract

Rat diet was supplemented with butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) or ethoxyquin (EQ) for 14 days, and hepatic microsomal epoxide hydratase (EH) and monooxygenase were subsequently studied in vitro. The antioxidants increased EH activity. The increase was marked with BHT (factor 3) and EQ (factor 4) and was paralleled by an increase in a protein band on SDS polyacrylamide gels which migrated together with purified rat hepatic EH. A slight but nonsignificant increase in cytochrome P450 content and a moderate increase in ethoxycoumarin deethylation and cytochrome b₅ content was also observed while aryl hydrocarbon hydroxylase (AHH) activity was not elevated. Irreversible binding of metabolically activated benzo(a)pyrene (BP) to calf thymus DNA was slightly reduced when catalyzed by antioxidant-stimulated microsomes. The cytochrome P450 population was similar to that found in phenobarbital (PB)-stimulated liver as jugded from preferential inhibition by and high affinity binding of metyrapone. The antioxidants also inhibited AHH activity in vitro in PB-stimulated microsomes, but not in 3-methyl-cholanthrene (MC)-stimulated microsomes.