MICROSOMAL PROTEIN SYNTHESIS AND INDUCTION OF CYTOCHROME P‐450 IN CIRRHOTIC RAT LIVER

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Abstract
In order to determine whether non-specific defects of protein synthesis account for reduced levels of cytochrome P-450 in cirrhotic liver, total microsomal protein synthesis and response to microsomal enzyme-inducing agents have been examined in rats. Cirrhosis was produced by administration of carbon tetrachloride (CCl4) and phenobarbitone for 10 weeks. Ten days after stopping these agents, cytochrome P-450 levels were 30% lower in cirrhotic liver than in controls (pin vivo by administration of [3H]-leucine, was similar in cirrhotic (1347 420 dpm/mg protein) and control (1317 303 dpm/mg protein) liver. Three separate types of microsomal enzyme-inducing agents, phenobarbitone, -naphthoflavone, and pregnenolone 16-carbonitrile, were administered to cirrhotic and normal rats. In both groups of animals increases of total cytochrome P-450 and selective changes of cytochrome P-450 isoenzymes (assessed by mixed function oxidase activity towards four substrates) were qualitatively and quantitatively similar. It is concluded that (1) hepalocytes of cirrhotic rat liver synthesize microsomal protein at a normal rate but less of it is cytochrome P-450, and (2) the entire process of enzyme induction is intact. Thus, it appears likely that altered regulation of basal levels of cytochrome P-450 rather than an altered response of the liver is responsible for the lowered cytochrome P-450 content of cirrhotic rat liver.

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