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

Abstract

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 (γ-TmT) that is rich in γ-tocopherol was used. Nrf2 knockout (Nrf2 -/-) and wild-type mice were maintained on 0.03, 0.1, or 0.3% γ-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 γ-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 γ-TmT between the Nrf2 (-/-) and the wild-type mice was observed. The γ-TmT treatment significantly increased the serum levels of γ- and δ-tocopherols. Interestingly, the serum levels of tocopherol metabolites, specifically the γ- and δ-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 γ-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.

• Authors: Guangxun Li, Mao-Jung Lee, Anna Ba Liu, Zhihong Yang, Yong Lin, Weichung Joe Shih, Chung S Yang
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 52 Issue 7 Pg. 1151-8 (Apr 01 2012) ISSN: 1873-4596 [Electronic] United States
• PMID: 22226829 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011. Published by Elsevier Inc.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Drinking Water
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• 8-epi-prostaglandin F2alpha
• 3-nitrotyrosine
• Tyrosine
• 8-Hydroxy-2'-Deoxyguanosine
• gamma-Tocopherol
• Dinoprost
• Leukocyte Common Antigens
• Ptprc protein, mouse
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Chromatography, High Pressure Liquid
• Colon (drug effects, metabolism)
• Deoxyguanosine (analogs & derivatives, metabolism)
• Dinoprost (analogs & derivatives, metabolism)
• Drinking Water
• Female
• Immunoenzyme Techniques
• Inflammation (drug therapy, metabolism)
• Leukocyte Common Antigens (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NF-E2-Related Factor 2 (physiology)
• Oxidative Stress (drug effects)
• Tyrosine (analogs & derivatives, metabolism)
• gamma-Tocopherol (pharmacology)