Effects of aspirin plus alpha-tocopherol on brain slices damage after hypoxia-reoxygenation in rats with type 1-like diabetes mellitus

Diabetes mellitus is a risk factor for cerebrovascular ischemic disease. Aspirin (acetylsalicylic acid) is the most widely used drug for the secondary prevention of thrombotic phenomena. It has been also recently demonstrated that alpha-tocopherol influenced in vitro the antiplatelet effect of aspirin. The aim of the present study is to evaluate the effects aspirin plus alpha-tocopherol on cerebral oxidative stress, prostaglandin production and the nitric oxide pathway in a model of hypoxia-reoxygenation in rat brain slices. Our results show an imbalance in brain oxidative status (reflected mainly as the increase in lipid peroxides) as a result of diabetes itself rather than a failure of the glutathione-based antioxidant system. Moreover, our results also show a higher concentration of prostaglandins in the brain of diabetic animals and a higher nitric oxide concentration, mainly through a high iNOS activity. After 180 min of post-hypoxia reoxygenation, LDH activity was 40.6% higher in animals with diabetes, in comparison to non-diabetic animals. The increase of the LDH efflux observed in non-treated rats was reduced by 31.2% with aspirin, by 34.7% with alpha-tocopherol and by 69.8% with the association aspirin-alpha-tocopherol. The accumulation of prostaglandin E-2 observed in diabetic non-treated rats was reduced statistically after the treatment with aspirin (34.2% inhibition), alpha-tocopherol (19.3% inhibition) or the association aspirin-a-tocopherol (54.4% inhibition). Nitric oxide production after 180 min reoxygenation was significantly reduced in aspirin (36.4%), alpha-tocopherol (22.7%) and aspirin-alpha-tocopherol (77.8%) treated rats with respect to diabetic non-treated animals; this was related mainly with a reduction in iNOS activity. The association between aspirin and alpha tocopherol could protects against brain ischemic-reperfusion damage with a better profile than aspirin alone. (c) 2006 Elsevier Ireland Ltd. All rights reserved.