TitleAlpha-tocopherol modulates Cyp3a expression, increases gamma-CEHC production, and limits tissue gamma-tocopherol accumulation in mice fed high gamma-tocopherol diets.
Publication TypeJournal Article
Year of Publication2005
AuthorsTraber MG, Siddens LK, Leonard SW, Schock B, Gohil K, Krueger SK, Cross CE, Williams DE
JournalFree Radic Biol Med
Date Published2005 Mar 15
Keywordsalpha-Tocopherol, Animal Feed, Animals, Antioxidants, Aryl Hydrocarbon Hydroxylases, Blotting, Western, Brain, Carrier Proteins, Chromans, Cytochrome P-450 CYP3A, gamma-Tocopherol, Genotype, Humans, Liver, Mice, Mice, Inbred C57BL, Mice, Transgenic, Oxidoreductases, N-Demethylating, Oxygen, Propionates, Time Factors, Vitamin E, Xenobiotics

Although all forms of vitamin E are absorbed, the liver preferentially secretes alpha-, but not gamma-tocopherol, into plasma. Liver alpha-tocopherol secretion is under the control of the alpha-tocopherol transfer protein (TTP). Therefore, to assess gamma-tocopherol bioactivities Ttpa-/-, +/- and +/+ mice were fed for 5 weeks diets containing gamma-tocopherol 550 (gamma-T550), gamma-tocopherol 60 (gamma-T60) mg/kg that also contained trace amounts of alpha-tocopherol, a vitamin E-deficient diet, or a control diet. Plasma and tissues from mice fed gamma-T550 diets were found to contain similar gamma- and alpha-tocopherol concentrations despite the high dietary gamma-tocopherol content; nervous tissues contained almost no gamma-tocopherol. Liver vitamin E metabolites (carboxyethyl hydroxychromans, CEHCs) were also measured. In mice with widely ranging liver alpha- (from 0.7 to 16 nmol/g) and gamma-tocopherol concentrations (0 to 13 nmol/g), hepatic alpha-CEHC was undetectable, but gamma-CEHC concentrations (0.1 to 0.8 nmol/g) were correlated with both alpha- and gamma-tocopherol concentrations (P < 0.004). Hepatic cytochrome P450s (CYPs) involved in vitamin E metabolism, Cyp4f and Cyp3a, were also measured. There were no variations in Cyp4f protein expression as related to diet or mouse genotype. However, Cyp3a was correlated (P < 0.0001) with liver alpha-, but not gamma-tocopherol concentrations. These data support the hypothesis that alpha-tocopherol modulates xenobiotic metabolism by increasing Cyp3a expression, gamma-CEHC formation, and the excretion of both gamma-tocopherol and gamma-CEHC.

Alternate JournalFree Radic. Biol. Med.
PubMed ID15721988
Grant ListDK59576 / DK / NIDDK NIH HHS / United States
ES011985 / ES / NIEHS NIH HHS / United States
P30 ES00210 / ES / NIEHS NIH HHS / United States