CFTR Potentiator Ivacaftor Protects Against Noise-Induced Hair Cell Loss by Increasing Nrf2 and Reducing Oxidative Stress

This study investigates the protective effects of the CFTR potentiator ivacaftor against noise-induced hair cell loss in FVB/NJ mice, mouse explant cultures, and HEI-OC1 cells. Noise exposure increases phosphorylation of CFTR at serine 737, leading to oxidative stress and hair cell damage. Ivacaftor pretreatment prevents this phosphorylation, maintains CFTR function, increases Nrf2 expression, reduces ROS formation, and attenuates hair cell and hearing loss. The protective effects of ivacaftor are nullified by the Nrf2 inhibitor ML385, highlighting the role of Nrf2 in redox homeostasis. Ivacaftor shows potential for treating noise-induced hearing loss by enhancing CFTR function and Nrf2 expression.