P-SIRT1/Nrf2 is linked to oxidative stress in alleviating hidden hearing loss

Abstract

Hidden hearing loss (HHL) is characterized by normal audiometric thresholds but impaired auditory function, particularly in noisy environments. Unfortunately, the unclear pathogenesis of HHL hinders accurate diagnosis and treatment. According to our research, audiological assessment of HHL mouse model showed a significant increase in the auditory brainstem response threshold, a decrease and delay in the I wave amplitude and latency, respectively, on the first day after noise exposure (NE). Histological observation showed a significant loss of ribbon synapses by immunofluorescence and stereocilia lodging by scanning electron microscopy. Furthermore, mice with HHL showed a significant oxidative stress damage, which was reduced by pretreatment with SRT1720 (SIRT1 specific agonist) through round-window injection. Additionally, cell experiments clarified that SRT1720 could reduce hydrogen peroxide-induced oxidative stress levels in House Ear Institute Organ of Corti cells and may be associated with activating the P-SIRT1/Nrf2 pathway. Subsequent experiments with Nrf2 knockdown confirmed the importance of this pathway. In conclusion, our findings highlight oxidative stress as the primary contributor to HHL, with the P-SIRT1/Nrf2 signaling pathway emerging as a promising therapeutic target for mitigating oxidative stress and alleviating HHL.