γ‐Tocopherol, but not α‐tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats

Abstract

γ-Tocopherol (γT), the major form of vitamin E in U.S. diets, and its physiological metabolite 2, 7, 8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman (γ-CEHC), in contrast to α-tocopherol (αT), 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 γT (33 or 100 mg/kg) and γ-CEHC (2 mg/pouch), but not αT (33 mg/kg), significantly reduced PGE₂ synthesis at the site of inflammation. γT, but not αT, significantly inhibited the formation of leukotriene B₄, a potent chemotactic agent synthesized by the 5-lipoxygenase of neutrophils. Although γT had no effect on neutrophil infiltration, it significantly attenuated the partial loss of food consumption caused by inflammation-associated discomfort. Administration of γT led consistently to a significant reduction of inflammation-mediated increase in 8-isoprostane, a biomarker of lipid peroxidation. γT at 100 mg/kg reduced TNF-α (65%;P=0.069), total nitrate/nitrite (40%;P=0.1), and lactate dehydrogenase activity (30%;P=0.067). Collectively, γT inhibits proinflammatory PGE₂ and LTB₄, decreases TNF-α, and attenuates inflammation-mediated damage. These findings provide strong evidence that γT shows anti-inflammatory activities in vivo that may be important for human disease prevention and therapy.—Jiang, Q., Ames, B. N. γ-Tocopherol, but not α-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats.