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

Abstract 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 Aβ 25–35. Cell viability, apoptosis, reactive oxygen species, and expression of antioxidative 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 Aβ 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 μM. Aβ 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 Aβ 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. Highlights • Edaravone resists Aβ 25–35 induced neurotoxicity in SHSY-5Y cells. • Edaravone alleviates Aβ 25–35 induced oxidative stress. • Edaravone rescues Nrf2 expression and nuclear translocation suppressed by Aβ 25–35. • Edaravone pretreatment elevates SOD and HO-1 levels in Aβ 25–35 exposed cells. [ABSTRACT FROM AUTHOR]