Regulatory mechanisms to control tissue alpha-tocopherol.
Regulatory mechanisms to control tissue alpha-tocopherol.
复制标题
控制组织α-生育酚的调节机制。
DOI：
10.1016/j.freeradbiomed.2007.05.027
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发表时间：
2007
影响因子：
7.4
通讯作者：
Traber,MaretG
中科院分区：
文献类型：
--
作者：
Mustacich,DebbieJ;Vo,AnhT;Elias,ValerieD;Payne,Katie;Sullivan,Laura;Leonard,ScottW;Traber,MaretG
To test the hypothesis that hepatic regulation of α-tocopherol metabolism would be sufficient to prevent overaccumulation of α-tocopherol in extrahepatic tissues and that administration of high doses of α-tocopherol would up-regulate extrahepatic xenobiotic pathways, rats received daily subcutaneous injections of either vehicle or 0.5, 1, 2, or 10 mg α-tocopherol/100 g body wt for 9 days. Liver α-tocopherol increased 15-fold in rats given 10 mg α-tocopherol/100 g body wt (mg/100 g) compared with controls. Hepatic α-tocopherol metabolites increased with increasing α-tocopherol doses, reaching 40-fold in rats given the highest dose. In rats injected with 10 mg/100 g, lung and duodenum α-tocopherol concentrations increased 3-fold, whereas α-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 α-tocopherol concentrations in extrahepatic tissues. Lung cytochrome P450 3A and 1A levels were unchanged by administration of α-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 α-tocopherol concentrations (R2=0.88, p<0.05). Increased lung MDR1 may provide protection from exposure to environmental toxins by increasing alveolar space α-tocopherol.
