EVALUATION OF SAFETY PROFILE AND CEREBROPROTECTIVE POTENTIAL OF DIMETHYL FUMARATE (DMF) AGAINST ISCHEMIA AND REPERFUSION INDUCED CEREBRAL INJURY IN WISTAR RATS

Abstract

Objective: Dimethyl fumarate (DMF) is the methyl ester of fumaric acid and used in the treatment of psoriasis, multiple sclerosis, etc. The present study was carried out to reveal safety as well as to find out the cerebro-protective potential of DMF against ischemia and reperfusion-induced cerebral injury in Wistar rats. Methods: Acute and sub-acute toxicity tests were performed in mice at various increasing doses of DMF as per OECD guidelines 420 and 407 respectively. The cerebral ischemia-reperfusion injury was induced by bilateral common carotid artery (BCCA) occlusion for 1 h and reperfusion for 5 h in Wistar rats. The DMF was administered orally at doses 10 mg/kg and 20 mg/kg for the assessment of its cerebro-protective potential by evaluating % infarction and % protection of cerebral tissue using TTC staining method. Results: The present study revealed that DMF is a safe drug as mortality was not observed in acute toxicity study up to 2000 mg/kg on oral administration, at the same time in sub-acute toxicity test DMF has showed no alteration in various parameters except a decrease in lymphocyte count. The DMF has shown a reduction in the % infarction. DMF at doses 10 mg/kg and 20 mg/kg has imparted 27.96±1.55% and 58.98±2.3% protection against ischemia and reperfusion-induced cerebral injury in Wistar rats. Conclusion: The DMF is the relatively safe drug with significant cerebro-protective potential.