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- W2148647566 endingPage "311" @default.
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- W2148647566 abstract "The xenobiotic response represents a complex group of chemical reactions aimed to inactivate and eliminate foreign chemicals, to antagonize their toxic effects, and to repair eventually damaged tissues. Intriguingly, xenobiotic response is also active against endogenous products of metabolism. Members of the nuclear receptor superfamily play a key role in xenobiotic detection and response. In particular, the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are transcription factors activated by a variety of endogenous and exogenous ligands. However, a high affinity endogenous ligand for CAR or PXR is not known, therefore these NRs have been put in the class of “orphan receptors”. Both CAR and PXR elevate the expression of the detoxification machinery in the presence of endogenous and exogenous ligands, regulating the expression of Phase I and II metabolizing enzymes and of phase III transporters. Unfortunately, prescription drugs are included in the list of xenobiotic recognized by CAR and PXR. Among others, statins represent a good example of CAR- and PXR-mediated drug metabolism. Indeed statins, the most effective and prescribed cholesterollowering drugs, are target of xenobiotic response mediated by CAR and PXR. Here, we review the structural and molecular bases of CAR- and PXR-mediated drug response highlighting how these mechanisms could impact on statin metabolism. Moreover, the alteration of statin pharmacodynamics and/or pharmacokinetics induced by concomitant drug treatment or dietary factors will be also examined. Keywords: CAR, cytochrome P450, PXR, orphan nuclear receptors, statin, xenobiotics, xenobiotic response, ligands, biotransformation, gastrointestinal tract" @default.
- W2148647566 created "2016-06-24" @default.
- W2148647566 creator A5007314231 @default.
- W2148647566 creator A5010844563 @default.
- W2148647566 creator A5062446429 @default.
- W2148647566 creator A5071553842 @default.
- W2148647566 creator A5079354466 @default.
- W2148647566 creator A5087673795 @default.
- W2148647566 date "2011-03-01" @default.
- W2148647566 modified "2023-10-17" @default.
- W2148647566 title "Xenosensors CAR and PXR at Work: Impact on Statin Metabolism" @default.
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