title: A combination of aspirin and gamma-tocopherol is superior to that of aspirin and alpha-tocopherol in anti-inflammatory action and attenuation of aspirin-induced adverse effects.
abstract: Nonsteroidal anti-inflammatory drugs such as aspirin are used for pain relief and chemoprevention against cancer, but frequently cause gastric mucosal injury. We examined whether combinations of aspirin and alpha-tocopherol (alphaT) or aspirin and gamma-tocopherol (gammaT), with alphaT and gammaT being the two major forms of vitamin E, are better anti-inflammatory agents than aspirin alone, and whether these combinations alleviate aspirin-associated side effects. In the carrageenan-induced air-pouch inflammation model in the rat, aspirin (150 mg/kg) or a combination of aspirin and gammaT (33 mg/kg) inhibited proinflammatory prostaglandin E(2) (PGE(2)) by 70% (P<.02) at the inflammation site 6 h after inflammation was initiated. However, at 18 h, only the combination decreased exudate volume (15%; P<.05) and showed modest inhibition of PGE(2) (40%; P<.07) and lactate dehydrogenase activity (30%; P=.07) in the fluid collected at the inflammation site. gammaT, but not alphaT, spared aspirin-induced reduction in food intake, partially reversed aspirin-depressed gastric PGE(2) and attenuated stomach lesions. Surprisingly, the combination of aspirin and alphaT (33 mg/kg) did not show more benefits than aspirin alone, but worsened gastric injury and food intake reduction. Our study demonstrated that a combination of aspirin and gammaT, but not a combination of aspirin and alphaT, has some advantage over aspirin alone in terms of anti-inflammatory effects and attenuation of aspirin-induced adverse effects. This combination may be useful in complementing aspirin in the treatment of chronic inflammatory conditions and cancer.
authors.affiliation: Department of Foods and Nutrition, Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907, USA. qjiang@purdue.edu
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.forename: Michelle
authors.initials: M
authors.lastname: Moreland
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Ames
authors.forename: Xinmin
authors.initials: X
authors.lastname: Yin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects; D002351:Carrageenan; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000627:therapeutic use; D024502:alpha-Tocopherol / Q000494:pharmacology*; D024504:gamma-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D024504:gamma-Tocopherol; D002351:Carrageenan; D015237:Dinoprost; D024502:alpha-Tocopherol; D015232:Dinoprostone; D001241:Aspirin