Dietary Cholesterol-Induced Enhancement of Hepatic Bio transformation Rate in Male Rats

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Abstract
Male rats were fed a cholesterol-free diet for 5 wk, followed by a 2% cholesterol diet for 4 wk. Another group of rats was continuously fed a cholesterol-free diet. A 3rd group was fed standard pellets during the whole experiment. Hepatic microsomal protein and cholesterol contents and drug-metabolizing enzyme activities were measured. The cholesterol-rich diet increased microsomal protein content and this increase disappeared after trypsin digestion of microsomal membranes. Microsomal cholesterol content was enhanced 3-fold by cholesterol feeding. Cytochrome P-450 concentration, NADPH cytochrome c reductase and aryl hydrocarbon hydroxylase activities showed only minor changes following cholesterol feeding. The p-nitroanisole O-demethylase and ethoxycoumarin deethylase activities were doubled by cholesterol in comparison to cholesterol-free diet. Trypsin digestion activated the UDP-glucuronosyltransferase enzyme 8- to 10-fold on a protein basis. Trypsin treatment increased the cholesterol activation of UDP-glucuronosyltransferase when compared to the activity in native microsomes. Apparently dietary cholesterol regulates the cholesterol content of microsomal membranes. The activities of drug-metabolizing enzymes are also altered, possibly due to the compositional changes of the membranes.