A combination of aspirin and gamma-tocopherol is better than that of aspirin and alpha-tocopherol in anti-inflammatory action and attenuating aspirin-caused adverse effects

摘要

Non-steroidal 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 (αT) or gamma-tocopherol (γT), two major forms of vitamin E, are better anti-inflammatories than aspirin alone and whether these combinations alleviate aspirin-associated side effects. In the carrageenan-induced air-pouch inflammation model in the rat, aspirin (150mg/kg) or a combination of aspirin and γT (33mg/kg) inhibited proinflammatory prostaglandin E2 (PGE2) by 70% (P<0.02) at the inflammation site at six hours after inflammation was initiated. But at 18 hours, only the combination decreased exudate volume (15%, P<0.05), and showed modest inhibition of PGE2 (40%, P<0.07) and lactate dehydrogenase activity (30%, P=0.07), in the fluid collected at the inflammation site. γT but not αT spared aspirin-caused reduction of food intake, partially reversed aspirin-depressed gastric PGE2 and attenuated stomach lesions. Surprisingly, the combination of aspirin and αT (33mg/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 γT, but not αT, has some advantage over aspirin alone in the anti-inflammatory effect and attenuation of the aspirin-caused adverse effect. This combination may be useful to complement aspirin in the treatment of chronic inflammatory conditions and cancer.