Titleα-Tocopherol injections in rats up-regulate hepatic ABC transporters, but not cytochrome P450 enzymes.
Publication TypeJournal Article
Year of Publication2011
AuthorsTraber MG, Labut EM, Leonard SW, Lebold KM
JournalFree Radic Biol Med
Date Published2011 Dec 01
Keywordsalpha-Tocopherol, Animals, ATP-Binding Cassette Transporters, Cytochrome P-450 Enzyme System, Hepatocytes, Male, Rats, Rats, Sprague-Dawley

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.

Alternate JournalFree Radic. Biol. Med.
PubMed ID21945367
PubMed Central IDPMC3208783
Grant ListR01 DK067930 / DK / NIDDK NIH HHS / United States
R01 DK067930-04 / DK / NIDDK NIH HHS / United States
DK067930 / DK / NIDDK NIH HHS / United States