Targeting dysregulation of redox homeostasis in noise-induced hearing loss: Oxidative stress and ROS signaling

Abstract

Hearing loss caused by exposure to recreational and occupational noise remains a worldwide disabling condition and dysregulation of redox homeostasis is the hallmark of cochlear damage induced by noise exposure. In this review we discuss the dual function of ROS to both promote cell damage (oxidative stress) and cell adaptive responses (ROS signaling) in the cochlea undergoing a stressful condition such as noise exposure. We focus on animal models of noise-induced hearing loss (NIHL) and on the function of exogenous antioxidants to maintaining a physiological role of ROS signaling by distinguishing the effect of exogenous "direct" antioxidants (i.e. CoQ₁₀, NAC), that react with ROS to decrease oxidative stress, from the exogenous "indirect" antioxidants (i.e. nutraceutics and phenolic compounds) that can activate cellular redox enzymes through the Keap1-Nrf2-ARE pathway. The anti-inflammatory properties of Nrf2 signaling are discussed in relation to the ROS/inflammation interplay in noise exposure. Unveiling the mechanisms of ROS regulating redox-associated signaling pathways is essential in providing relevant targets for innovative and effective therapeutic strategies against NIHL.

Keywords: Acoustic trauma; Antioxidants; Cochlea; Inflammation; NF-κB; Nrf2/HO-1 pathway; Phenolic compounds; ROS.