Neuroprotective Efficacy of Edaravone against Arsenic-Induced Behavioral and Neurochemical Deficits in Rats: Amelioration of Cholinergic and Mitochondrial Functions

Background: A substantial amount of evidence indicates that long-term arsenic exposure leads to various types of pathological complications, especially cognitive dysfunction. Objective: The present study was designed to assess the neuroprotective potential of edaravone (a potent free radical scavenger) against arsenic-induced neurotoxicity in Wistar rats. Methods: Adult male Wistar rats were randomly divided into five groups. Arsenic (20 mg/kg/day; p.o.) and Edaravone (5 and 10 mg/kg/day; i.p.) were administered in different experimental groups for 28 days. Results: The results of various behavioral test paradigms revealed that arsenic caused significant learning and memory deficits, along with anxiety-like behavior. In biochemical analysis, we found marked elevations of oxidative-nitrosative stress (indicated by augmentation of lipid peroxidation and nitrite) and a reduction of glutathione levels in the hippocampus and frontal cortex region of arsenic-treated rats. Moreover, arsenic administration caused mitochondrial complexes impairment and reduction of acetylcholinesterase level. On the other hand, chronic treatment with edaravone (10 mg/kg) significantly ameliorated the arsenic-induced behavioral deficits and neurochemical anomalies. Conclusion: This study suggests that edaravone confers neuroprotection against arsenic-induced memory impairment and anxiety-like behavior, which may be attributed to the inhibition of oxidative-nitrosative stress and amelioration of cholinergic and mitochondrial functions.