A combination of aspirin and γ-tocopherol is superior to that of aspirin and α-tocopherol in anti-inflammatory action and attenuation of aspirin-induced adverse effects

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 (alpha T) or aspirin and gamma-tocopherol (gamma T), with alpha T and gamma T 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 gamma T (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 PGE2 (40%; P<.07) and lactate dehydrogenase activity (30%; P=.07) in the fluid collected at the inflammation site. gamma T, but not alpha T, spared aspirin-induced reduction in food intake, partially reversed aspirin-depressed gastric PGE2 and attenuated stomach lesions. surprisingly, the combination of aspirin and alpha T (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 gamma T, but not a combination of aspirin and aT, 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. (C) 2009 Elsevier Inc. All rights reserved.