Enhancement of Hepatic Drug Metabolism with Dietary Cholesterol in the Rat

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Abstract
The effect of dietary cholesterol on the biochemical composition and on the activities of drug metabolizing enzymes in the rat liver was studied. There were no statistically significant differences in the measured microsomal macrocomponents between the reference group on fat free diet and the experimental rats on 5 % cholesterol diet. However, there were marked changes in the fatty acid composition of microsomal phospholipids. The activities of cytochrome c reductase, cytochrome P–450 and p–nitroanisole o–demethylase were increased significantly during cholesterol feeding. The activitiy of aryl hydrocarbon hydroxylase remained unaffected. The activity of hepatic UDPglucuronosyltransferase was also increased very significantly with dietary cholesterol. It may be true that cholesterol affects the activities of drug metabolizing enzymes partly via changes in the membrane structure, but cholesterol may also act as an inducing compound.

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