Vitamin E, nuclear receptors and xenobiotic metabolism.
Supplemental vitamin E (alpha-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.
Traber
Maret G
MG
Linus Pauling Institute, Oregon State University, Corvallis, 97331-6512, USA. maret.traber@oregonstate.edu
D000818:Animals; D000975:Antioxidants / Q000009:adverse effects; D006801:Humans; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000009:adverse effects
D000975:Antioxidants; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D015262:Xenobiotics; D014810:Vitamin E; D024502:alpha-Tocopherol