Title | α-Tocopherol injections in rats up-regulate hepatic ABC transporters, but not cytochrome P450 enzymes. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Traber, M, Labut, EM, Leonard, SW, Lebold, KM |
Journal | Free radical biology & medicine |
Volume | 51 |
Issue | 11 |
Pagination | 2031-40 |
Date Published | 2011 Dec 1 |
Keywords | Rats, Sprague-Dawley |
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. |
DOI | 10.1016/j.freeradbiomed.2011.08.033 |