Effects of aging and caloric restriction on hepatic drug metabolizing enzymes in the Fischer 344 rat. I: The cytochrome P-450 dependent monooxygenase system

Abstract The effects of long-term caloric restriction on the hepatic cytochrome P -450 dependent monooxygenase system were investigated in the 22-month-old Fischer 344 rat. Caloric restriction decreased the age-related changes in hepatic testosterone metabolism, which are associated with demasculinization of the liver. Caloric restriction also increased hepatic microsomal testosterone 6β-hydroxylase, lauric acid 12-hydroxylase and 4-nitrophenol hydroxylase activities over corresponding values in both ad libitum fed 22-month and 60-day-old control male rats. This suggests that cytochrome P -450 isozymes, P-450 pcn 1&2 , P-452 and P450 j may be induced by caloric restriction. Such changes in cytochrome P -450 isozyme profiles could result in altered carcinogen activation, radical formation or drug detoxication in the calorically restricted rat.