Effect of synthetic antioxidants on hydrogen peroxide formation, oxyferro cytochrome P-450 concentration and oxygen consumption in liver microsomes.

Synthetic antioxidants lead in vitro to increased H2O2 formation in rat liver and lung microsomes and in guinea pig and hamster liver microsomes. Butylated hydroxyanisole and ethoxyquin are more potent than propyl-, octyl-, and dodecyl gallate; butylated hydroxytoluene is only weakly active. Extra production of H2O2 is maximal at antioxidant concentrations between 50 and 500 microM and is dependent on the concentration of NADPH. It is paralleled by increased microsomal oxygen consumption and decreased concentration of oxycytochrome P-450 and is enhanced by pretreatment of the animals with phenobarbital. Both the endogenous and the antioxidant-stimulated H2O2 production are inhibited by metyrapone. In vivo administration of ethoxyquin and butylated hydroxyanisole in the diet leads to decreased oxycytochrome P-450 concentrations but not to increased H2O2 formation in liver microsomes. No extra production of H2O2 was observed in a glucose oxidase or xanthine oxidase system; rather, inhibition occurred in the latter system. Our data suggest that antioxidants enhance the oxidase function of cytochrome P-450. This effect is discussed in view of the known toxicity of these food additives.