Dietary cholesterol-induced changes of xenobiotic metabolism in liver. I. Influence of xenobiotic administration on hepatic membrane structure.

We have studied the effects of dietary lipids on the structure and function of hepatic endoplasmic reticulum by feeding rats either with a 2% cholesterol or cholesterol-free diet. Rats were further administered either phenobarbitone, carbon tetrachloride, or both in combination to reveal possible differences in the response of the microsomal membranes to xenobiotics. Cholesterol feeding increased the membrane cholesterol contents and also carbon tetrachloride increased microsomal cholesterol contents in those rats fed a cholesterol-free diet. Also the microsomal phospholipid contents were higher in those rats fed 2% cholesterol diet than in those fed cholesterol-free diet and in the 2% cholesterol group also phenobarbitone increased the phospholipid contents. In addition, there were changes in the phospholipid-fatty acid proportions between rats fed 2% cholesterol and cholesterol-free diets. When 1,8-ANS was used as a fluorescence probe, phenobarbitone increased the fluorescence in both the dietary groups, while carbon tetrachloride decreased it; less change was present using PNA as a substrate. When Scatchard plots were constructed phenobarbitone changed the turning point more in the cholesterol-free group than in the 2% cholesterol group, while reversed orders of changes were found with carbon tetrachloride. The results demonstrated that dietary cholesterol has profound effects on the structure of microsomal membranes far beyond changes in their cholesterol content. The membrane fluidity also changes owing to alterations in the phospholipid contents and in their fatty acid composition.