Inducibility of mucosal drug-metabolizing enzymes of rats fed on a cholesterol-rich diet by polychlorinated biphenyl, 3-methylcholanthrene and phenobarbitone.
The results show that a cholesterol-rich diet changes the composition of mucosal membranes. A high cholesterol diet increases mucosal cholesterol and phospholipid contents. Cholesterol enhanced mucosal NADPH cytochrome c reductase and aryl hydrocarbon hydroxylase activities as well as mucosal UDP glucuronosyltransferase activity. When phenobarbitone or Clophen A 50 or 60 were administered intraperitoneally to cholesterol-fed rats, the hydroxylation and glucuronidation activities decreased to a lower level. 3-Methylcholanthrene was, however, able to maintain or increase mucosal hydroxylative enzymes and UDP glucuronosyltransferase. These results indicate that the drug-metabolizing enzymes of the intestinal mucosa behave very differently from those in the liver. Diet apparently has a regulatory effect on the induction of drug-metabolizing enzymes because only a very potent inducer, 3-methylcholanthrene, was able to maintain and even induce mucosal drug-metabolizing enzymes in rats fed on a high cholesterol diet, possibly through changes in the microenvironment of enzymes caused by cholesterol.
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects*; D014453:Glucuronosyltransferase / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002791:Cholesterol, Dietary; D010743:Phospholipids; D011506:Proteins; D008748:Methylcholanthrene; D002784:Cholesterol; D011078:Polychlorinated Biphenyls; D009251:NADPH-Ferrihemoprotein Reductase; D014453:Glucuronosyltransferase; D010634:Phenobarbital