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(The FASEB Journal. 2003;17:816-822.)
© 2003 FASEB

{gamma}-Tocopherol, but not {alpha}-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats

QING JIANG and BRUCE N. AMES1

Division of Biochemistry and Molecular Biology, University of California, Berkeley; and Children's Hospital Oakland Research Institute, Oakland, California, USA

1Correspondence: CHORI, 5700 Martin Luther King Jr. Way, Oakland, CA 94609-1673, USA. E-mail: bnames{at}uclink4.berkeley.edu

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


Key Words: vitamin E • {gamma}-tocopherol metabolite • prostaglandin E2 • leukotriene B4 • TNF-alpha




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