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Regulatory mechanisms to control tissue alpha-tocopherol.
|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 radical biology & medicine|
|Date Published||2007 Aug 15|
|Keywords||alpha-Tocopherol, Animals, Antioxidants, Blotting, Western, Cytochrome P-450 Enzyme System, Intestines, Kidney, Liver, Lung, Male, P-Glycoprotein, Rats, Rats, Sprague-Dawley, Spinal Cord|
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.
|Alternate Journal||Free Radic. Biol. Med.|