TitleAlpha-tocopherol regulation of hepatic cytochrome P450s and ABC transporters in rats.
Publication TypeJournal Article
Year of Publication2006
AuthorsMustacich DJ, Leonard SW, Devereaux MW, Sokol RJ, Traber MG
JournalFree Radic Biol Med
Date Published2006 Oct 01
Keywordsalpha-Tocopherol, Animals, ATP-Binding Cassette Transporters, Chromans, Cytochrome P-450 Enzyme System, Injections, Subcutaneous, Liver, Liver Extracts, Male, Models, Molecular, Propionates, Rats, Rats, Sprague-Dawley, Time Factors

To test the hypothesis that supra-elevated hepatic alpha-tocopherol concentrations would up-regulate mechanisms that result in increased hepatic alpha-tocopherol metabolism and excretion, rats received daily subcutaneous alpha-tocopherol injections (10 mg/100 g body wt) and then were sacrificed on Day 0 or 12 h following their previous injection on Days 3, 6, 9, 12, 15, and 18. Liver alpha-tocopherol concentrations increased from 12 +/- 1 nmol/g (mean +/- SE) to 819 +/- 74 (Day 3), decreased at Day 9 (486 +/- 67), and continued to decrease through Day 18 (338 +/- 37). alpha-Tocopherol metabolites and their intermediates increased and decreased similarly to alpha-tocopherol albeit at lower concentrations. There were no changes in known vitamin E regulatory proteins, i.e., hepatic alpha-tocopherol transfer protein or cytochrome P450 (CYP) 4F. In contrast, both CYP3A and CYP2B, key xenobiotic metabolizing enzymes, doubled by Day 6 and remained elevated, while P450 reductase increased more slowly. Consistent with the decrease in liver alpha-tocopherol concentrations, a protein involved in biliary xenobiotic excretion, p-glycoprotein, increased at Day 9, doubling by Day 15. Thus hepatic alpha-tocopherol concentrations altered hepatic proteins involved in metabolism and disposition of xenobiotic agents.

Alternate JournalFree Radic. Biol. Med.
PubMed ID16962932
Grant ListDK38446 / DK / NIDDK NIH HHS / United States
DK59576 / DK / NIDDK NIH HHS / United States
P30 ES00210 / ES / NIEHS NIH HHS / United States