N ACETYL CYSTEINE ALLEVIATES PHENYTOIN INDUCED BEHAVIORAL ABNORMALITIES IN RATS

NAC being an antioxidant combats oxidative stress induced by phenytoin, thereby hypothesized to reduce phenytoin induced behavioral abnormalities. The influence of N acetyl cysteine (NAC) supplementation on phenytoin induced behavioral abnormalities was investigated. Male Wistar rats were divided into 5 groups and each group received vehicle (0.2% CMC), Phenytoin (20mg/Kg), Phenytoin co administered with three graded doses of NAC (50, 100, 200 mg/kg) in 0.2% CMC for 45 days. Motor coordination, exploratory behavior, memory and spontaneous motor activity were evaluated by Rota rod, Hole board, Elevated plus maze and Actophotometer respectively. On day 45, regional brain lipid peroxidation, acetylcholinesterase (ACh E) activity and histopathological studies were performed after euthanasia. In addition, pharmacokinetic and pharmacodynamic drug interactions between phenytoin and NAC were also studied. Long term administration of phenytoin induced behavioral abnormalities, elevated regional brain malondialdehyde (MDA) and ACh E activity, also revealed congestion in addition to damaged cells in brain regions. NAC significantly prevented phenytoin induced behavioral abnormalities, oxidative stress and reversed the histopathological abnormalities. There were no significant differences in the serum levels of phenytoin and the degree of protection offered by phenytoin in NAC supplemented groups revealing that there were no pharmacokinetic and pharmacodynamic interactions between phenytoin and NAC. This study demonstrates that NAC is effective in preventing phenytoin induced behavioral abnormalities and oxidative stress in rats without altering the serum phenytoin levels and its therapeutic effect. This suggests the potential of adjuvant NAC therapy in alleviating behavioral disturbances induced by chronic phenytoin therapy.