Edaravone inhibits neuronal ferroptosis and alleviates acute Central nervous system injury induced by diquat enhancement of METTL14-mediated m6A methylation of Aldh1l1.
The biological effects of edaravone (Eda), a free radical scavenger, include anti-inflammatory, antioxidant, and neuroprotective qualities. Nevertheless, the function and potential mechanisms of Eda in central nervous system injury damage are still unknown. A rat model of acute diquat toxicity was constructed to observe the pathological changes in brain tissues after diquat administration. The changes of mitophagy and ferroptosis in PC12 cells were assessed to the protective activity of Eda. To assess the methylation levels of m6A RNA, the EpiQuik m6A RNA Methylation Quantification Kit was utilized. RIP, dual luciferase reporter assay and mRNA stability detection confirm the relationship between METTL14 and Aldh11l1. Knockdown and overexpression experiments were performed to determine the effects of METTL14 and Aldh1l1 on rats and PC12 cells stimulated with diquat under Eda treatment. Eda dramatically ameliorated diquat-induced central nervous system injury. Eda notably attenuated apoptosis, pro-inflammatory cytokines activation, and oxidative stress damage in diquat-induced rats. Eda significantly suppressed apoptosis, mitophagy and ferroptosis after diquat-stimulated PC12 cells. Mitophagy inhibitor Mdivi-1 reversed the induction of ferroptosis effects of diquat via decreased Fe2+ content and increased Ca2+ level. knockdown of METTL14 reversed the therapeutic effect of Eda on diquat-induced injury. Eda promoted METTL14-mediated Aldh1l1 m6A methylation and alleviates acute central nervous system injury induced by diquat in vivo and in vitro. Eda has a protective effect on diquat-induced nervous system injury, and its mechanism may be related to the activation of m6A modification of Aldh11l1 by METTL14 and the inhibition of mitophagy and. ferroptosis.
