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

Abstract

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 E2 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-alpha-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.

• Authors: J A González-Correa, M M Arrebola, A L Cansino, J Muñoz-Marín, A Guerrero, F Sánchez de la Cuesta, J P De la Cruz
• Journal: Neuroscience letters (Neurosci Lett) Vol. 400 Issue 3 Pg. 252-7 (Jun 12 2006) ISSN: 0304-3940 [Print] Ireland
• PMID: 16545519 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antioxidants
• Drug Combinations
• Neuroprotective Agents
• Platelet Aggregation Inhibitors
• alpha-Tocopherol
• Aspirin

Topics

• Animals
• Antioxidants (administration & dosage)
• Aspirin (administration & dosage)
• Brain Ischemia (complications, diagnosis, metabolism, prevention & control)
• Cells, Cultured
• Diabetes Mellitus, Type 1 (complications, diagnosis, drug therapy, metabolism)
• Drug Combinations
• Male
• Neuroprotective Agents (administration & dosage)
• Platelet Aggregation Inhibitors (administration & dosage)
• Rats
• Rats, Wistar
• Reperfusion Injury (complications, diagnosis, metabolism, prevention & control)
• Treatment Outcome
• alpha-Tocopherol (administration & dosage)