Title | Regulatory mechanisms to control tissue alpha-tocopherol. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Mustacich DJ, Vo AT, Elias VD, Payne K, Sullivan L, Leonard SW, Traber MG |
Journal | Free Radic Biol Med |
Volume | 43 |
Issue | 4 |
Pagination | 610-8 |
Date Published | 2007 Aug 15 |
ISSN | 0891-5849 |
Keywords | alpha-Tocopherol, Animals, Antioxidants, ATP Binding Cassette Transporter, Subfamily B, Member 1, Blotting, Western, Cytochrome P-450 Enzyme System, Intestinal Mucosa, Intestines, Kidney, Liver, Lung, Male, Rats, Rats, Sprague-Dawley, Spinal Cord |
Abstract | To test the hypothesis that hepatic regulation of alpha-tocopherol metabolism would be sufficient to prevent overaccumulation of alpha-tocopherol in extrahepatic tissues and that administration of high doses of alpha-tocopherol would up-regulate extrahepatic xenobiotic pathways, rats received daily subcutaneous injections of either vehicle or 0.5, 1, 2, or 10 mg alpha-tocopherol/100 g body wt for 9 days. Liver alpha-tocopherol increased 15-fold in rats given 10 mg alpha-tocopherol/100 g body wt (mg/100 g) compared with controls. Hepatic alpha-tocopherol metabolites increased with increasing alpha-tocopherol doses, reaching 40-fold in rats given the highest dose. In rats injected with 10 mg/100 g, lung and duodenum alpha-tocopherol concentrations increased 3-fold, whereas alpha-tocopherol concentrations of other extrahepatic tissues increased 2-fold or less. With the exception of muscle, daily administration of less than 2 mg/100 g failed to increase alpha-tocopherol concentrations in extrahepatic tissues. Lung cytochrome P450 3A and 1A levels were unchanged by administration of alpha-tocopherol at any dose. In contrast, lung P-glycoprotein (MDR1) levels increased dose dependently and expression of this xenobiotic transport protein was correlated with lung alpha-tocopherol concentrations (R(2)=0.88, p<0.05). Increased lung MDR1 may provide protection from exposure to environmental toxins by increasing alveolar space alpha-tocopherol. |
DOI | 10.1016/j.freeradbiomed.2007.05.027 |
Alternate Journal | Free Radic. Biol. Med. |
PubMed ID | 17640571 |
PubMed Central ID | PMC2693716 |
Grant List | R01 DK059576 / DK / NIDDK NIH HHS / United States R01 DK067930 / DK / NIDDK NIH HHS / United States R01 DK067930-01A1 / DK / NIDDK NIH HHS / United States DK 067930 / DK / NIDDK NIH HHS / United States |