Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats.

Abstract

Gamma-tocopherol (gammaT), the major form of vitamin E in U.S. diets, and its physiological metabolite 2, 7, 8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), in contrast to alpha-tocopherol (alphaT), the primary vitamin E in supplements, inhibit cyclooxygenase-catalyzed synthesis of prostaglandin E2 (PGE2) in activated macrophages and epithelial cells. Here we report that in carrageenan-induced inflammation in male Wistar rats, administration of gammaT (33 or 100 mg/kg) and gamma-CEHC (2 mg/pouch), but not alphaT (33 mg/kg), significantly reduced PGE2 synthesis at the site of inflammation. gammaT, but not alphaT, significantly inhibited the formation of leukotriene B4, a potent chemotactic agent synthesized by the 5-lipoxygenase of neutrophils. Although gammaT had no effect on neutrophil infiltration, it significantly attenuated the partial loss of food consumption caused by inflammation-associated discomfort. Administration of gammaT led consistently to a significant reduction of inflammation-mediated increase in 8-isoprostane, a biomarker of lipid peroxidation. gammaT at 100 mg/kg reduced TNF-alpha (65%;P=0.069), total nitrate/nitrite (40%;P=0.1), and lactate dehydrogenase activity (30%;P=0.067). Collectively, gammaT inhibits proinflammatory PGE2 and LTB4, decreases TNF-alpha, and attenuates inflammation-mediated damage. These findings provide strong evidence that gammaT shows anti-inflammatory activities in vivo that may be important for human disease prevention and therapy.

• Authors: Qing Jiang, Bruce N Ames
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 17 Issue 8 Pg. 816-22 (May 2003) ISSN: 1530-6860 [Electronic] United States
• PMID: 12724340 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antioxidants
• Chromans
• Eicosanoids
• Nitrates
• Nitrites
• Propionates
• Tumor Necrosis Factor-alpha
• 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman
• Leukotriene B4
• gamma-Tocopherol
• Carrageenan
• alpha-Tocopherol
• Dinoprostone

Topics

• Animals
• Antioxidants (pharmacology)
• Carrageenan
• Chromans (blood, metabolism, pharmacology)
• Dinoprostone (metabolism)
• Dose-Response Relationship, Drug
• Eating (drug effects)
• Eicosanoids (metabolism)
• Exudates and Transudates (drug effects, metabolism)
• Inflammation (chemically induced, metabolism, pathology)
• Leukotriene B4 (metabolism)
• Lipid Peroxidation (drug effects)
• Male
• Neutrophil Infiltration (drug effects)
• Nitrates (metabolism)
• Nitrites (metabolism)
• Propionates (blood, metabolism, pharmacology)
• Rats
• Rats, Wistar
• Tumor Necrosis Factor-alpha (drug effects, metabolism)
• alpha-Tocopherol (blood, metabolism, pharmacology)
• gamma-Tocopherol (blood, metabolism, pharmacology)