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Free Radic Biol Med. 2011 Dec 1;51(11):2031-40. doi: 10.1016/j.freeradbiomed.2011.08.033. Epub 2011 Sep 3.

α-Tocopherol injections in rats up-regulate hepatic ABC transporters, but not cytochrome P450 enzymes.

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  • 1Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. maret.traber@oregonstate.edu

Abstract

The role of hepatic xenobiotic regulatory mechanisms in modulating hepatic α-tocopherol concentrations during excess vitamin E administration remains unclear. We hypothesized that increased hepatic α-tocopherol would cause a marked xenobiotic response. Thus, we assessed cytochrome P450 oxidation systems (phase I), conjugation systems (phase II), and transporters (phase III) after daily α-tocopherol injections (100mg/kg body wt) for up to 9days in rats. α-Tocopherol injections increased hepatic α-tocopherol concentrations nearly 20-fold, along with a 10-fold increase in the hepatic α-tocopherol metabolites α-CEHC and α-CMBHC. Expression of phase I (CYP3A2, CYP3A1, CYP2B2) and phase II (SULT2A1) proteins and/or mRNAs was variably affected by α-tocopherol injections; however, expression of phase III transporter genes was consistently changed by α-tocopherol. Two liver efflux transporter genes, ABCB1b and ABCG2, were up-regulated after α-tocopherol injections, whereas OATP, a liver influx transporter, was down-regulated. Thus, an overload of hepatic α-tocopherol increases its own metabolism and increases expression of genes of transporters that are postulated to lead to increased excretion of both vitamin E and its metabolites.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21945367
[PubMed - indexed for MEDLINE]
PMCID:
PMC3208783
Free PMC Article

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