Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 52, Issue 7, Pages 1151-1158Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2011.12.005
Keywords
Antioxidant; Inflammation; Nrf2(-/-); Tocopherols; Tocopherol metabolites
Funding
- NIH [CA122474, CA129015, CA133021]
- Share Facilities [ES05022, CA072720]
- John L. Colaizzi Endowed Chair
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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 (gamma-TmT) that is rich in gamma-tocopherol was used. Nrf2 knockout (Nrf2 -/-) and wild-type mice were maintained on 0.03, 0.1, or 0.3% gamma-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 gamma-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 gamma-TmT between the Nrf2 (-/-) and the wild-type mice was observed. The gamma-TmT treatment significantly increased the serum levels of gamma- and delta-tocopherols. Interestingly, the serum levels of tocopherol metabolites, specifically the gamma- and delta-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 gamma-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. (C) 2011 Published by Elsevier Inc.
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