Effect of aging on response to induction and metabolizing activity of the hepatic mixed-function oxidase system of male Sprague–Dawley rats
The composition and activity of the rat hepatic mixed-function oxidase system were investigated, in male rats 17 to 127 weeks old, with respect to content of its various components and their response to induction by phenobarbital and β-naphthoflavone. There were decreases in many of the components of this enzyme system in older rats which could not be fully compensated by phenobarbital induction. However, there appeared to be no age-related loss of response to induction by β-naphthoflavone. Decreases in mixed-function oxidase enzymes with age did not occur at the same rate or to the same extent. Metabolic studies with ethylmorphine and aniline demonstrated some age-associated changes which did not necessarily parallel reductions in the enzyme system. For example, there was a reduction in apparent Km as a function of age for the hydroxylation of aniline in rats treated with β-naphthoflavone, even though they showed no apparent change in the amount of cytochrome P-450. There was also a trend to altered Km for the demethylation of ethylmorphine in saline or corn oil treated rats in older animals. We feel that these changes are a reflection of differential reductions in the various isozymes of cytochromes P-450. Further studies are planned to confirm this hypothesis.
Chromosomal assignments of genes coding for components of the mixed-function oxidase system in mice. Genetic localization of the cytochrome P-450PCN and P-450PB gene families and the nadph-cytochrome P-450 oxidoreductase and epoxide hydratase genes.