Dietary cholesterol-induced enhancement of hepatic biotransformation rate in male rats

Pharmacology. 1978;17(3):163-72. doi: 10.1159/000136850.

Abstract

Male rats were fed a cholesterol-free diet for 5 weeks, followed by a 2% cholesterol diet for 4 weeks. Another group of rats was continuously fed a cholesterol-free diet. A third group was fed standard pelllets 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 three-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 eight- to ten-fold on a protein basis. Trypsin treatment increased the cholesterol activation of UDP-glucuronosyltransferase when compared to the activity in native microsomes. The data suggest that 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biotransformation / drug effects
  • Body Weight / drug effects
  • Cholesterol, Dietary / pharmacology*
  • Kinetics
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Membranes / metabolism
  • Microsomes, Liver / enzymology
  • Mixed Function Oxygenases / metabolism
  • Organ Size / drug effects
  • Pentobarbital / pharmacology
  • Proteins / metabolism
  • Rats
  • Sleep / drug effects
  • Time Factors

Substances

  • Cholesterol, Dietary
  • Proteins
  • Mixed Function Oxygenases
  • Pentobarbital