Edaravone reduces Aβ-induced oxidative damage in SH-SY5Y cells by activating the Nrf2/ARE signaling pathway

Aims: Edaravone potentially alleviates cognitive deficits in a mouse model of Alzheimer's disease (AD). However, the mechanism of edaravone in suppressing AD progression remains unclear. We aim to investigate the mechanism of edaravone in suppressing oxidative stress-mediated AD progression in vitro. Main methods: Human neuroblastoma SH-SY5Y cells were pretreated with different concentrations of edaravone prior to the induction by A beta(25-35). Cell viability, apoptosis, reactive oxygen species, and expression of anti-oxidative response elements (ARE) including Nrf2, SOD, and HO-1 were assessed. Key findings: The results showed that apoptosis and reactive oxygen species levels significantly increased in A beta(25-35)-treated cells, whereas the mRNA and protein levels of Nrf2, SOD and HO-1 decreased. The opposite changes were observed in cells that were pre-treated with edaravone, particularly at a concentration of 40 mu M. A beta(25-35)-treatment suppressed Nrf2 expression and nuclear translocation were rescued by Edaravone. Genetic inhibition of Nrf2 greatly decreased the protective effect of edaravone against cell apoptosis and cytotoxicity induced by A beta(25-35), accompanied by decreases in SOD and HO-1 expression. Significance: Activation of the Nrf2/ARE signaling pathway may underlie the protective effects of edaravone against the oxidative damage associated with Alzheimer's disease.