[Crosstalk between cholesterol homeostasis and drug metabolism].
Nowadays cardiovascular diseases are among the major causes of mortality in the developed world. High cholesterol level in blood and atherosclerosis play the main role in progression of cardiovascular diseases. Reducing serum cholesterol level has been shown to avoid deleterious effects, whereas in serious diseases it improves the outcome. A widely used, statin-based therapy induces a decrease in de novo cholesterol biosynthesis in the liver. Another possibility for lowering serum cholesterol level is to block the uptake of dietary cholesterol from intestine (e.g. ezetimibe). Coadministration of statins and cholesterol uptake inhibitors provides an efficient therapeutical strategy. Several therapeutic agents, reducing serum cholesterol level, are able to regulate the expression of not only cholesterogenic enzymes, but of the major drug metabolizing enzymes, cytochromes P450. The crosstalk between cholesterol homeostasis and drug metabolism is mediated by nuclear receptors, activating target genes in response of endogenous and exogenous ligands. Better understanding of the crosstalk between cholesterol homeostasis and drug metabolism is essential for developing an adequate strategy in therapy and in novel drug development.
Kohalmy
Krisztina
K
Magyar Tudományos Akadémia, Kémiai Kutatóközpont Farmakobiokémiai Osztály Budapest.
Rozman
Damjana
D
Pascussi
Jean-Marc
JM
Sárváry
Eniko
E
Monostory
Katalin
K
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism*; D001384:Azetidines / Q000627:therapeutic use; D001646:Bile / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D000069438:Ezetimibe; D025461:Feedback, Physiological; D006706:Homeostasis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D008099:Liver / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D020239:Receptor Cross-Talk / Q000187:drug effects*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
D000924:Anticholesteremic Agents; D001384:Azetidines; D002791:Cholesterol, Dietary; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D004364:Pharmaceutical Preparations; D018160:Receptors, Cytoplasmic and Nuclear; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D000069438:Ezetimibe