Edaravone Protects HT22 Neurons from H2O2‐induced Apoptosis by Inhibiting the MAPK Signaling Pathway

Summary Aims Oxidative stress is frequently implicated in the pathology of neurodegenerative diseases. This study aimed to investigate the effects and their underlying mechanism(s) of edaravone upon hydrogen peroxide (H 2 O 2 )–induced oxidative stress and apoptosis in HT 22 cells, a murine hippocampal neuronal model. Methods HT 22 cells were treated with H 2 O 2 in the presence of various concentrations of edaravone or in its absence. A CCK ‐8 assay, Hoechst 33342 staining, and flow cytometry were used to detect cytotoxicity and apoptosis. In addition, the levels of reactive oxygen species ( ROS ) and the expression of Bcl‐2, Bax, p‐ ERK 1/2, p‐ JNK , and p‐P38 proteins in HT 22 cells were examined. Results Exogenous H 2 O 2 decreased cell viability in a concentration‐dependent manner and was associated with increased apoptosis and ROS production. Moreover, H 2 O 2 significantly activated and upregulated the expression of p‐ ERK 1/2, p‐ JNK , and p‐P38, while edaravon protected HT 22 cells against H 2 O 2 ‐induced injury by inhibiting the production of ROS and activating the MAPK signaling pathway. Conclusions Our results provide the first evidence that edaravone can protect H 2 O 2 ‐induced cell injury in HT 22 neurons via its antioxidant action. These findings suggest that edaravone may be useful in the treatment of neurodegenerative disorders in which oxidative stress has been principally implicated.