Edaravone prevents memory impairment in diabetic rats: Role of oxidative stress

Abstract

BackgroundUncontrolled diabetes mellitus (DM) is accompanied by progressive cognitive deterioration mediated by neurodegeneration due to chronic hyperglycemia and subsequent oxidative damage. Oxidative stress damage due to high blood glucose is associated with functional and structural changes in the hippocampus, responsible for cognitive properties, leading to cognitive impairment. Edaravone is a potent antioxidant with neuroprotective properties that has mainly been used to treat amyotrophic lateral sclerosis and has been tested in many models associated with cognition deficits. Our study aimed to assess edaravone's potential neuroprotective activity to reverse memory impairment in a streptozotocin (STZ)-induced diabetic rat model. MethodsDM was induced by a single 50 mg/kg STZ intraperitoneal injection. Rats received edaravone intraperitoneally at 6 mg/kg/day, six days/week, for four weeks. The radial arm water maze behavioral test evaluated both learning and memory. Oxidative stress was evaluated by molecularly measuring hippocampus enzyme activities and biomarker levels. ResultsImpairment of short- and long-term memory was observed in rats with STZ-induced diabetes, accompanied by decreased hippocampal superoxide dismutase and glutathione peroxidase activities and reduced/oxidized glutathione ratio. Edaravone significantly attenuated memory impairment (p < 0.05) and normalized oxidative stress biomarker levels (p < 0.05). Furthermore, STZ significantly increased hippocampal thiobarbituric acid reactive substance activity, which was also normalized by edaravone treatment (p < 0.05). However, STZ and edaravone did not affect catalase and brain-derived neurotrophic factor levels (p > 0.05). ConclusionEdaravone prevented STZ-induced memory impairment and attenuated oxidative stress likely by restoring hippocampus antioxidant mechanisms.