Autophagy Induction by Mangiferin Protects Auditory Hair Cells from Ototoxicity

Oxidative stress is a major cause of auditory hair cell degeneration and hearing impairment.Reducing intracellular reactive oxygen species (ROS) levels may help preserve auditory hair cell function. In this study, we explored the otoprotective properties of mangiferin, a xanthonoid extracted from mango leaves, bark, and fruit peels. Our findings indicate that mangiferin protects HEI-OC1 cells against oxidative stress induced by H₂O₂ through modulation of autophagic mechanisms and elimination of ROS. The modulation of proteins linked to autophagy and apoptosis, such as LC3 conversion and SQSTM1 degradation, confirmed this protective effect. Furthermore, auditory brainstem response test and scanning electron microscopy findings indicated that mangiferin effectively mitigates hair cell degeneration in the organ of Corti in guinea pigs subjected to ototoxicity induced by kanamycin and furosemide. Immunohistochemical analysis also provided insights into the effects of mangiferin on ribbon synapses within the cochlea of rats. Both in vitro and in vivo studies demonstrated that mangiferin exerts protective effect against ototoxicity by inducing autophagy.