Hearing loss is the most common
sensory disorder in humans, and a significant number of cases is due to the
ototoxicity of drugs such as
cisplatin that cause hair cell (HC) damage. Thus, there is great interest in finding agents and mechanisms that protect HCs from ototoxic drug damage. It has been proposed that epigenetic modifications are related to inner ear development and play a significant role in HC protection and HC regeneration; however, whether the
m6A modification and the ethyl
ester form of
meclofenamic acid (MA2), which is a highly selective inhibitor of FTO (fatmass and
obesity-associated
enzyme, one of the primary human demethylases), can affect the process of HC apoptosis induced by ototoxic drugs remains largely unexplored. In this study, we took advantage of the HEI-OC1 cell line, which is a cochlear HC-like cell line, to investigate the role of epigenetic modifications in
cisplatin-induced cell death. We found that
cisplatin injury caused
reactive oxygen species accumulation and increased apoptosis in HEI-OC1 cells, and the
cisplatin injury was reduced by co-treatment with MA2 compared to the
cisplatin-only group. Further investigation showed that MA2 attenuated
cisplatin-induced oxidative stress and apoptosis in HEI-OC1 cells. We next found that the
cisplatin-induced upregulation of autophagy was significantly inhibited after MA2 treatment, indicating that MA2 inhibited the
cisplatin-induced excessive autophagy. Our findings show that MA2 has a protective effect and improves the viability of HEI-OC1 cells after
cisplatin treatment, and they provide new insights into potential therapeutic targets for the amelioration of
cisplatin-induced
ototoxicity.