Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats.
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.
Division of Biochemistry and Molecular Biology, University of California, Berkeley; and Children's Hospital Oakland Research Institute, Oakland, California 94609-1673, USA.
Qing
Q
Jiang
Bruce N
BN
Ames
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002351:Carrageenan; D002839:Chromans / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D015777:Eicosanoids / Q000378:metabolism*; D005122:Exudates and Transudates / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007975:Leukotriene B4 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011422:Propionates / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D024502:alpha-Tocopherol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D024504:gamma-Tocopherol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*
D000975:Antioxidants; D002839:Chromans; D015777:Eicosanoids; D009566:Nitrates; D009573:Nitrites; D011422:Propionates; D014409:Tumor Necrosis Factor-alpha; C107690:2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman; D007975:Leukotriene B4; D024504:gamma-Tocopherol; D002351:Carrageenan; D024502:alpha-Tocopherol; D015232:Dinoprostone