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Vitamin E, nuclear receptors and xenobiotic metabolism

2003; Elsevier BV; Volume: 423; Issue: 1 Linguagem: Inglês

10.1016/j.abb.2003.10.009

1096-0384

Maret G. Traber,

Pharmacogenetics and Drug Metabolism

Supplemental vitamin E (α-tocopherol) is taken daily by more than 35 million people in the US. Following absorption and liver uptake, the fate of vitamin E is largely unknown. Of potential importance are recent clinical studies that have reported adverse effects of vitamin E that may be directly related to its hepatic metabolism. In an in vitro system, both vitamin E and rifampicin, a known stimulator of xenobiotic metabolism, activated the pregnane X receptor (PXR), an orphan nuclear receptor. PXR as a heterodimer with the retinoid X receptor (RXR), binds to specific cis-elements in the promoter regions of genes. PXR/RXR regulates a constellation of genes involved in xenobiotic detoxification, including oxidation, conjugation, and transporters. Importantly, PXR/RXR regulates the cytochrome P450 (CYP), CYP3A, involved in the hepatic detoxification of more than 50% of prescription drugs. Vitamin E acting as a PXR ligand could alter these PXR-mediated reactions. Unfortunately, the extent to which pharmacologic doses of vitamin E modulate these pathways in vivo has not been determined.