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Effect of Cholesterol Feeding on Tissue Lipid Peroxidation, Glutathione Peroxidase Activity and Liver Microsomal Functions in Rats and Guinea Pigs¹

Human Nutrition Program, School of Public Health, The University of Michigan, Ann Arbor, Michigan 48109

The effect of cholesterol feeding on liver and aortic non-enzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was added to a casein-sucrose-soybean oil basal diet for rats or a stock diet with 2% soybean oil for guinea pigs. The effect of vitamin E and cholestyramine was also examined in some experiments. Cholesterol feeding increased the rate of lipid peroxidation in liver and aortic homogenate both in rats and guinea pigs when fed non-vitamin E supplemented basal diets. Vitamin E supplementation prevented the increase in the aorta, but not as completely in the liver in rats, while the reverse was true in guinea pigs. The effect of cholestyramine was dependent on the level of vitamin E in the diet. Cholesterol feeding decreased glutathione peroxidase activities in rats and guinea pigs. In guinea pigs, cholesterol feeding also markedly decreased liver microsomal NADPH-dependent lipid peroxidation, codein hydroxylation and cytochrome P-450 levels especially when fed non-vitamin E supplemented basal diets. In rats, cholesterol feeding reduced liver microsomal NADPH-dependent lipid peroxidation and in some cases, increased microsomal codeine hydroxylation activities, but had no effect on microsomal cytochrome P-450 levels. Vitamin E supplementation increased liver and serum cholesterol levels in guinea pigs, but had no such effect in rats. Results of this study indicate that cholesterol feeding can result in various metabolic alterations in rats and guinea pigs. The implication of these alterations in atherogenesis requires further investigations.

KEY WORDS: • cholesterol feeding • tissue lipid peroxidation • glutathione peroxidase • microsomal NADPH-dependent lipid peroxidation • microsomal codeine hydroxylation • microsomal cytochrome P-450 • vitamin E • aorta

¹ The work was supported in part by a Grant-inaid from the Michigan Heart Association.

² Present address: G. M. Thie, Department of Human Nutrition, Agricultural University, Wageningen, The Netherlands.

Manuscript received 24 May 1976.