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MICROSOMAL PROTEIN SYNTHESIS AND INDUCTION OF CYTOCHROME P‐450 IN CIRRHOTIC RAT LIVER
Author(s) -
Farrell Geoffrey C,
Zaluzny Louise
Publication year - 1984
Publication title -
australian journal of experimental biology and medical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0004-945X
DOI - 10.1038/icb.1984.29
Subject(s) - microsome , cytochrome , carbon tetrachloride , cirrhosis , medicine , cytochrome p450 , oxidase test , endocrinology , microsoma , cytochrome c oxidase , enzyme inducer , enzyme , chemistry , biology , biochemistry , organic chemistry
Summary 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 (CCl 4 ) and phenobarbitone for 10 weeks. Ten days after stopping these agents, cytochrome P‐450 levels were 30% lower in cirrhotic liver than in controls (p<0·0001). However, total microsomal protein synthesis, determined in vivo by administration of [ 3 H]‐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, β‐naphthoflavone, and pregnenolone 16α‐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.