Edaravone inhibits procaspase‐3 denitrosylation and activation through FasL‐Trx2 pathway in KA‐induced seizure

Abstract Previous studies have demonstrated that excessive free radicals play an essential role in the initiation and progression of epilepsy and that a novel exogenous free radical scavenger edaravone (Ed) exerts some neuroprotective effects on seizure‐induced neuronal damage. The purpose of this study was to elucidate the possible molecular mechanisms of Ed associated with procaspase‐3 denitrosylation and activation through the FasL‐Trx2 pathway in seizures rats. In this study, we investigated the effects of Ed on the regulation of the combination of Fas ligand/Fas receptor and the major components of the death‐inducing signaling complex (DISC) in the hippocampus of kainic acid (KA)‐treated Sprague Dawley (SD) rats. Treatment with Ed can attenuate the increased expression of FasL induced by KA and prevent procaspase‐3 denitrosylation and activation via suppression of the FasL‐Trx2 signaling pathway, which alleviates the neuronal damage in seizures. These results provide experimental evidence that Ed functions by preventing the denitrosylation and activation of procaspase‐3 and that Ed acts as a therapeutic option for epilepsy.