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Alterations in Hepatic Microsomal Mixed-Function Oxidase System during Different Levels of Food Restriction in Adult Male and Female Rats

Drug Metabolism Laboratory, Biochemistry Division, Department of Chemistry, Marathwada University, Aurangabad 431004, India

Wistar strain adult male and female rats were given 25, 50 and 75% less food than an ad libitum-fed group of rats for 45 d and the effects of food restriction on hepatic drug metabolizing enzymes, microsomal electron transport components, NADPH-dependent lipid peroxidation and glutathione-S-transferase activities were studied. Compared to ad libitum-fed controls, the cytochrome P-450 levels were higher in food restricted male rats, while they were lower in food restricted females. The activities of NADPH cytochrome c reductase were lower in food restricted females than in ad libitum-fed controls. The activities of drug metabolizing enzymes, aminopyrine N-demethylase and acetanilide hydroxylase were higher in food restricted males, whereas in food restricted females these activities were lower than in respective groups fed ad libitum. Microsomal, NADPH-dependent lipid peroxidation was higher in 25 and 50% food restricted females while in 50 and 75% food restricted males it was lower than in ad libitum controls of the same sex. The cytosolic glutathione-S-transferase activities were lower in food restricted rats of both the sexes than in the same sexed controls. Another group of male and female rats were given 75% less food than the ad libitum-fed rats and refed for 3 d prior to killing. Here also, the effects of restriction were different between sexes. It is concluded that hepatic microsomal mixed-function oxidase system (MFOS) is altered due to feed restriction and food restriction followed by refeeding, in a sex-related manner.

KEY WORDS: • food restriction • drug metabolizing enzymes • cytochrome P-450 • sex difference

¹ Present address: Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610.

² To whom correspondence should be addressed. R. S. H. and A. M. S. are grateful to CSIR and U.G.C., India, respectively for financial support.

Manuscript received 26 August 1985. Revision accepted 8 November 1985.