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.