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

FASEB J. 2003 May;17(8):816-22. doi: 10.1096/fj.02-0877com.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • 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