Formation of inhibitors of lipid peroxidation during oxidative metabolism of hydrophobic xenobiotics catalyzed by mixed function oxygenases.

It was shown that benz (alpha) pyrene inhibits the NADPH-dependent lipid peroxidation (LPO) in rat liver microsomes in vitro. The degree of LPO inhibition is correlated with the accumulation of hydroxylated derivatives of benz (alpha) pyrene in the presence of NADPH. Benz (alpha) pyrene protects cytochrome P-450 against conversion into its inactive form, P-420, induced by LPO. Another inhibitor of the NADPH-dependent LPO in rat liver microsomes is chlorpromazine. Inhibition of LPO is due to the antioxidant effect of hydroxylated derivatives of chlorpromazine formed in the course of its metabolism by NADPH-dependent microsomal oxygenase. NADPH-dependent formation of hydroxylated metabolites of chlorpromazine, possessing antioxidant properties, was also estimated in brain cortex microsomes from rats and men. It is shown that chlorpromazine when preliminarily injected to rats, protects against LPO activation in brain tissue in vivo induced by exposure of the animals to hyperbaric oxygenation.