Author/Editor		Režen, Tadeja
Title		The impact of cholesterol and its metabolites on drug metabolism
Type		članek
Source		Expert Opin Drug Metab Toxicol
Vol. and No.		Letnik 7, št. 4
Publication year		2011
Volume		str. 387-98
Language		eng
Abstract		Introduction: Global prevalence of Western-type diet has increased in the last decades resulting in occurrence of certain chronic diseases. This type of diet is also linked to high-cholesterol intake and increase in blood cholesterol. Many of the molecular mechanisms of dealing with increased levels of cholesterol and its metabolites have been elucidated in animal models and humans. It is also evident that cholesterol metabolism is closely connected to drug metabolism. Cholesterol/bile acids and drugs share many transporters, enzymes and regulatory proteins which are key points in the crosstalk. Areas covered: This review presents an overview of the effect of cholesterol and its metabolites on drug metabolism with special emphasis on speciesspecific differences. The article focuses on the role of nuclear receptors farnesoid X receptor, vitamin D receptor and liver X receptor in the regulation of drug metabolism genes and the role of cholesterol biosynthesis intermediates, oxysterols and bile acids in the induction of drug metabolism through pregnane X receptor. Expert opinion: Studies show that the regulation of drug metabolism by sterols is multileveled. Many species-dependent differences were observed which hinder the transfer of findings from model animals to humans. As of now, there is little evidence available for cholesterol impact on drug metabolism in vivo in humans. There is also the need to confirm the results obtained in animal models and in vitro analyses in human cells but this is very difficult given the current lack of tools.
Descriptors		CHOLESTEROL BILE ACIDS AND SALTS CHOLESTEROL, DIETARY HYPERCHOLESTEROLEMIA METABOLIC DETOXICATION, DRUG DRUG INTERACTIONS DISEASE MODELS, ANIMAL MICE, INBRED C57BL