Phenytoin is used widely in the treatment of epilepsy. The drug produces haematological toxicities such as thrombocytopenia, leukopenia, neutropenia, agranulocytosis, pancytopenia, hemolytic anemia and aplastic anemia. The arene oxide metabolites of phenytoin are expected to cause stem cell death leading to hematological disturbances via oxidative stress. The objective of the study is to investigate the dose dependent effect of vitamin C supplementation on oxidative stress and haematotoxicity induced by chronic administration of phenytoin (20 mg/kg, p.o) for a period of 45 days. On 45th day of phenytoin and phenytoin plus vitamin C treatment, blood was withdrawn from retro orbital plexus of rats and was subjected to estimation of hematological parameters, enzymatic, non enzymatic antioxidants, total antioxidant status and lipid peroxidation. Vitamin C supplementation significantly increased the total RBCs, haemoglobin, total WBCs, platelets and packed cell volume which was decreased by phenytoin, in a dose dependent manner. Vitamin C improved the activities of SOD, catalase and augmented the levels of reduced glutathione, vitamin C, total antioxidants and thereby reversed the oxidative stress induced by phenytoin. Vitamin C prevented oxidative stress and hematologic impairment induced by phenytoin possibly through its ability to scavenge reactive oxygen species. These findings are of interest in view of the high prevalence of hematological side-effects and oxidative stress associated with the long term phenytoin therapy.
Key Words: Phenytoin, ascorbic acid, oxidative stress, antioxidants, haematotoxicity.