Relation of Ca++ accumulation and lipid peroxidation with CCl4-induced toxicity in the rat liver.

The relationship between lipid peroxidation and Ca++ content in liver and hepatic cellular disruption was studied in 24 hr-fasted rats. Microsomal lipid peroxidation of livers in rats treated with a single dose of 16 mg or 96 mg CCl4/kg was significantly increased by 22% or 49% as measured by the diene conjugation technique. Ca++ content of liver microsomes in rats treated with 96 mg CCl4/kg was significantly increased by 20%, while the Ca++ content in rats treated with 16 mg CCl4/kg was not changed. On the other hand mitochondrial Ca++ content was tremendously increased in both rats treated with 16 mg and 96 mg CCl4/kg. Furthermore, when the activity of plasma glutamic pyruvic transaminase (GPT), which is a liver-specific enzyme, was investigated 3 hr after CCl4 treatment, hepatotoxicity was evident in rats treated with 96 mg/kg but not evident in rats treated with 16 mg/kg. These results indicate that there was a good correlation between the microsomal Ca++ content and the hepatic cellular disruption but no correlation between the microsomal lipid peroxidation and the hepatic cellular disruption as measured by the diene conjugation.