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 E 2 (PGE 2 ) 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 PGE 2 synthesis at the site of inflammation. γT, but not αT, significantly inhibited the formation of leukotriene B 4 , 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 PGE 2 and LTB 4 , 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. FASEB J. 17, 816–822 (2003)