Protective Effect of Edaravone on Cyclophosphamide Induced Oxidative Stress and Neurotoxicity in Rats

Background: Cyclophosphamide (CPA) is the most widely prescribed cancer chemotherapeutic agent which shows serious neurotoxic side effect. Generation of reactive oxygen species at the cellular level is the basic mechanism of cyclophosphamide induced neurotoxicity. Edaravone is the synthetic drug used for brain stroke and has potent antioxidant property. Objective: This study aimed to investigate the effect of edaravone on neurobehavioral and neuropathological alteration induced by cyclophosphamide in male rats. Methods: Twenty eight Sprague-Dawley rats were equally divided into four groups of seven rats in each. The control group received saline, and other groups were given CPA intraperitoneally (100 mg/kg), CPA (100 mg/kg) intraperitoneally + Edaravone (10 mg/kg) orally, or Edaravone (10 mg/kg) orally for one month. Results: Our data showed that CPA significantly elevated brain AChE activity in the hippocampal region. A decrease in the total antioxidant capacity and a reduction in the CAT, SOD, and GPX activity occurred in the brains of the rats exposed to CPA. CPA-treated rats showed a significant impairment in long-term-memory and motor coordination. These results were supported by histopathological observations of the brain. Results revealed that administration of edaravone reversed AChE activity alternation and ameliorated behavioral and histopathological changes induced by CPA. Conclusion: This study suggests that co-administration of edaravone with cyclophosphamide may be a useful intriguing therapeutic approach to overcome cyclophosphamide induced neurotoxicity.