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Age-related changes in liver drug-metabolizing enzymes

1980; Elsevier BV; Volume: 15; Issue: 4 Linguagem: Inglês

10.1016/0531-5565(80)90037-6

1873-6815

Douglas L. Schmucker, Rose K. Wang,

Metabolism and Genetic Disorders

The non-induced levels of hepatic microsomal NADPH cytochrome c reductase and cytochrome P-450 undergo marked age-dependent declines in male Fischer rats, especially between maturity and senescence. Phenobarbital administration causes significant increases in these two parameters in young (1 month) and mature (16 months) animals, but not in senescent rats (27 months). Both the rates of enzyme and hemoprotein induction and the maximum-induced levels achieved after 6 days of drug treatment are significantly greater in the young and mature animals vs the senescent rats. These functional data correlate reasonably well with (1) a similar age-dependent response of microsomal protein concentration to phenobarbital administration and (2) the quantitative morphological evidence demonstrating an age-related loss in the amount of hepatic smooth surfaced endoplasmic reticulum between maturity and senescence.