|Title||Vitamin E, nuclear receptors and xenobiotic metabolism.|
|Publication Type||Journal Article|
|Year of Publication||2004|
|Journal||Arch Biochem Biophys|
|Date Published||2004 Mar 01|
|Keywords||alpha-Tocopherol, Animals, Antioxidants, Humans, Pregnane X Receptor, Receptors, Cytoplasmic and Nuclear, Receptors, Steroid, Vitamin E, Xenobiotics|
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.
|Alternate Journal||Arch. Biochem. Biophys.|