بررسي تاثير آنتي اكسيدانها بر بعضي عوارض ناشي از مصرف مزمن فني تويين در مدلهاي حيواني

The effects of antioxidants on some of the side effects of models

Oxidative stress is one of the known in vivo effects of phenytoin that could account for some of its side effects: Previous studies have shown a strong correlation between phenytoin free radicals induceds damage and its teratogenicity. In this study, the role of this pro-oxidative property in some other side effects of phenytoin has been investigated. Phenytoin sodium, or its vehicle, distilled water, was chronically administrated to groups of mice and rats by gastric gavage. Two hours before phenytoin administration, the animals also received one of the antioxidants: a-tocopherol acetate, ascorbic acid, sodium selenite or their vehicles, distilled water or olive oil, through the same route. At the end of chronic treatment period, the responsiveness of animals to myorelaxant effect of pancuronium, anesthetic activity of urethane and ketamine, serum sugar as well as transaminase levels and prothrombin time were examined. Chronic phenytoin treatment resulted in a significant resistance to pancuronium and urethane effects, while no difference in other measured parameters was observed between phenytoin received and respective control groups. Supplementation with any of the mentioned antioxidants significantly reversed the phenytoin-induced alterations in animalʹs responsiveness to pancuronium and urethane. Therefore phenytoin induced oxidative stress is a major contributor to at least some of its side effects and, antioxidants supplementation seems worthy to be investigated as a novel approach for reducing side effects of this drug.