Protective effects of dithiol malonate derivatives on carbon tetrachloride induced hepatotoxicity in primary culture of adult rat hepatocytes

Abstract

The effect of Dithiol Malonate Derivatives (DMDs) on microsomal enzyme activities, protein and RNA synthesis, and hepatotoxicity induced by carbon tetrachloride were invesdtigated in primary culture of adult rat hepatocytes. DMDs had no effect on total cytochrome P-450 content and associated drug metabolizing enzyme activities, such as ethoxycoumarin O-deethylasee, aryl hydrocarbon hydroxylase. Also, DMNDs had no effect on protein and RNA synthesis in primary culture of rat hepatocytes. Protective effects of DMDs on hepatotoxicities induced by carbon tetrachloride, such as LDH release, lipid peroxidation, fatty liver (accumulation of triacylglyceride), inhibition of protein synthesis were studied. DMDs showed protective effect on LDH release and DMDs supressed the increased peroxidation produced by carbon tetrachloride. It was found that DMDs had protective effect on the accumulation of cellular triacylglycerol produced by carbon tetrachloride and on the inhibitory action of carbon tetrachloride on triacylglycerol secretion. Although DMDs recovered the protein synthesis decreased by carbon tetrachloride.