The antioxidant and anti-inflammatory activities of tocopherols are independent of Nrf2 in mice

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• 作者：Guangxun Li^a ; Mao-Jung Lee^a ; Anna Ba Liu^a ; Zhihong Yang^a ; Yong Lin^b ; ^c ; Weichung Joe Shih^b ; ^c ; Chung S. Yang^a ; ^c ; ^{csyang@pharmacy.rutgers.edu}
• 关键词：纬-TmT ; gamma-tocopherol-rich mixture of tocopherols ; 纬-T ; gamma-tocopherol ; Nrf2 ; nuclear factor (erythroid-derived 2)-like 2 ; Nrf2 (-/-) ; Nrf2 knockout ; DSS ; dextran sulfate sodium ; AOM ; azoxymethane ; PGE2 ; prostaglandin E2 ; RONS ; reactive oxygen and n
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 期刊代码：105_08915849
• 类别：med
• 出版时间：1 April, 2012
• 卷：52
• 期：7
• 页码：1151-1158
• 文件大小：1891 K

摘要

The present study investigated the antioxidant and anti-inflammatory actions of tocopherols in mice and determined whether the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is involved in these activities. A mixture of tocopherols (纬-TmT) that is rich in 纬-tocopherol was used. Nrf2 knockout (Nrf2 -/-) and wild-type mice were maintained on 0.03, 0.1, or 0.3%纬-TmT-enriched diet starting 2 weeks before the administration of dextran sulfate sodium (DSS) in drinking water (for 1 week, to induce colonic inflammation), until the termination of the experiment at 3 days after the DSS treatment. Dietary 纬-TmT dose dependently lowered the levels of 8-oxo-deoxyguanosine, nitrotyrosine, inflammation index, and leukocyte infiltration in colon tissues, as well as 8-isoprostane and prostaglandin E2 in the serum, in both Nrf2 (-/-) and wild-type mice. No significant difference on the inhibitory actions of 纬-TmT between the Nrf2 (-/-) and the wild-type mice was observed. The 纬-TmT treatment significantly increased the serum levels of 纬- and 未-tocopherols. Interestingly, the serum levels of tocopherol metabolites, specifically the 纬- and 未-forms of carboxymethylbutyl hydroxychroman and carboxyethyl hydroxychroman, in Nrf2 (-/-) mice were significantly higher than those in wild-type mice. These findings suggest that the antioxidant and anti-inflammatory activities of 纬-TmT in the colon are mostly due to the direct action of tocopherols in trapping reactive oxygen and nitrogen species, independent of the antioxidant enzymes and anti-inflammatory proteins that are regulated by Nrf2; however, Nrf2 knockout appears to affect the serum levels of tocopherol metabolites.