Microsomal mixed-function oxidase activity and senescence—II. In vivo and in vitro hepatic drug metabolism in rats of different ages following partial hepatectomy

Abstract

The duration of hexobarbital hypnosis was determined in CFN male rats of different ages, and hexobarbital-induced sleep time was found to increase with advancing age. Partial hepatectomies were then performed on the rodents, and in vitro zoxazolamine hydroxylase activity was found to decline in the senescent rats, thereby confirming previous studies. Identical experimental parameters were determined after restoration of the excised liver mass. The duration of hexobarbital sleep time increased for animals of all ages, while zoxazolamine hydroxylase remained unchanged. Thus, the rate of hepatic drug metabolism in old animals was not increased in the presence of newly generated liver cells. These results are consistent with the hypothesis that age-related alterations in the mixed-function oxidase system are not a result of primary aging changes in the hepatic cells themselves, but are compensatory changes resulting from alterations in other tissues.