The effect of cirrhosis of the liver on microsomal detoxications and cytochrome P-450.

Cirrhosis has been produced in rats by a combination of carbon tetrachloride (CCl(4)) and phenobarbitone administration. Hepatic microsomal cytochrome P-450 contents have been measured during the production of cirrhosis, and in established cirrhosis, after recovery from the acute effects of CCl(4) has taken place. Cytochrome P-450 levels fall after CCl(4) dosage but recover rapidly to near normal values in the early stages of the regime although later on they remain at a low level. In rats given 8 weeks to recover from the acute effects of the cirrhosis-producing regime, P-450 and pyramidon demethylation levels remained depressed in the more severely cirrhotic animals. The response to the inducing effect of phenobarbitone was diminished also. Liver water remained high in the more severely cirrhotic rats, but was near normal in those with less severe lesions. The basis of the changes observed is discussed and the features of experimental cirrhosis and clinical cirrhosis in man are compared.