Rat liver microsomal lipid peroxidation produced during the oxidative metabolism of ethacrynic acid

Thiobarbituric acid reactive substances (TBARS) were produced in rat liver microsomal suspension incubated with ethacrynic acid (loop diuretic drug) a nd NADPH. Two oxidative metabolites of ethacrynic acid with dicarboxylic ac id and hydroxylated ethyl group, respectively were formed in the reaction m ixture. The oxidative metabolism of ethacrynic acid was inhibited by cytoch rome P450 inhibitors. The formation of TEARS was remarkably depressed by in hibitors like diethyldithiocarbamate and disulfiram. These results indicate that lipid peroxidation occurred in rat liver microsomes through the oxida tive metabolism of ethacrynic acid.