Increase of lipid hydroperoxides in liver mitochondria and inhibition of cytochrome oxidase by carbon tetrachloride intoxication in rats.

The cellular localization of lipid hydroperoxides was determined for the first time in mitochondria, microsomes and cytosol of rat liver using a specific method involving chemical derivatization and HPLC. Mitochondria contained the highest level of hydroperoxides. After 6h of intragastric administration of carbon tetrachloride (CCl4) to rats (2 ml/kg body weight), the concentration of lipid hydroperoxides increased significantly in liver mitochondria and cytochrome oxidase activity was inhibited to 35% of the control rats. The mitochondrial content of haem a decreased to 60% of the control at 12h of CCl4 administration. In vitro reaction of mitochondria with CCl4 caused inactivation of cytochrome oxidase. These observations suggested that cytochrome oxidase and haem a in mitochondria were targets of CCl4.