Modification of microsomal membrane components and induction of hepatic drug biotransformation in rats on a high cholesterol diet

Lang, Matti, Laitinen, Matti, Hietanen, Eino and Vainio, Harri (1976) Modification of microsomal membrane components and induction of hepatic drug biotransformation in rats on a high cholesterol diet. Acta Pharmacologica et Toxicologica, 39 2: 273-288.


Author Lang, Matti
Laitinen, Matti
Hietanen, Eino
Vainio, Harri
Title Modification of microsomal membrane components and induction of hepatic drug biotransformation in rats on a high cholesterol diet
Journal name Acta Pharmacologica et Toxicologica   Check publisher's open access policy
ISSN 0001-6683
Publication date 1976-08
Sub-type Article (original research)
Volume 39
Issue 2
Start page 273
End page 288
Total pages 16
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Abstract The effect of cholesterol on the microsomal membrane components and the induction of drug–metabolizing enzymes was studied in rats after feeding with a two per cent cholesterol diet and administration of phenobarbitone or 3–methylcholanthrene intraperitoneally. The results revealed that cholesterol affected both the amount and the binding properties of protein, phospholipid and cholesterol in microsomes. Cholesterol also modified the effects of phenobarbitone and 3–methylcholanthrene on microsomal membranes. The administration of inducers increased the liver–body weight ratio significantly. Phenobarbitone enhanced NADPH cytochrome c reductase activity in native microsomes by about 2–fold. The aryl hydrocarbon hydroxylase activity was increased markedly by both phenobarbitone and 3–methylcholanthrene. The UDPglucuronosyltrans–ferase activity was also enhanced by both inducers. After trypsin digestion of microsomes UDPglucuronosyltransferase activity was significantly higher in rats on a high cholesterol diet than in those on standard diet. After treating the microsomes in vitro by various membrane perturbants it was found that 3–methylcholanthrene made the enzyme proteins less soluble than phenobarbitone. The results support the idea that cholesterol affects the activities of drug metabolizing enzymes, due to changes in the structure of microsomal membranes.
Keyword Drug metabolism
Induction
Cholesterol
Microsomes
Membrane structure
Rat
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Title continues Basic & Clinical Pharmacology & Toxicology (0001-6683)

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
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Created: Mon, 30 Nov 2009, 15:05:51 EST