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

ABSTRACT: The role of hepatic xenobiotic regulatory mechanisms in modulating hepatic ?-tocopherol concentrations during excess vitamin E administration remains unclear. We hypothesized that increased hepatic ?-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 ?-tocopherol injections (100mg/kg body wt) for up to 9days in rats. ?-Tocopherol injections increased hepatic ?-tocopherol concentrations nearly 20-fold, along with a 10-fold increase in the hepatic ?-tocopherol metabolites ?-CEHC and ?-CMBHC. Expression of phase I (CYP3A2, CYP3A1, CYP2B2) and phase II (SULT2A1) proteins and/or mRNAs was variably affected by ?-tocopherol injections; however, expression of phase III transporter genes was consistently changed by ?-tocopherol. Two liver efflux transporter genes, ABCB1b and ABCG2, were up-regulated after ?-tocopherol injections, whereas OATP, a liver influx transporter, was down-regulated. Thus, an overload of hepatic ?-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.

SUBMITTER: Traber MG

PROVIDER: S-EPMC3208783 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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

Traber Maret G MG Labut Edwin M EM Leonard Scott W SW Lebold Katie M KM

Free radical biology & medicine 20110903 11

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 ...[more]

PMID: 21945367

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Dataset Information

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

Publications

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

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