Noise-Induced Cochlear Damage Involves PPAR Down-Regulation through the Interplay between Oxidative Stress and Inflammation.

Fabiola Paciello,Gaetano Paludetti,Rolando Rolesi,Jacopo Galli,Anna Rita Fetoni,Diana Troiani,Anna Pisani,Claudio Grassi,Vincent Escarrat

doi:10.3390/antiox10081188

Abstract

The cross-talk between oxidative stress and inflammation seems to play a key role in noise-induced hearing loss. Several studies have addressed the role of PPAR receptors in mediating antioxidant and anti-inflammatory effects and, although its protective activity has been demonstrated in several tissues, less is known about how PPARs could be involved in cochlear dysfunction induced by noise exposure. In this study, we used an in vivo model of noise-induced hearing loss to investigate how oxidative stress and inflammation participate in cochlear dysfunction through PPAR signaling pathways. Specifically, we found a progressive decrease in PPAR expression in the cochlea after acoustic trauma, paralleled by an increase in oxidative stress and inflammation. By comparing an antioxidant (Q-ter) and an anti-inflammatory (Anakinra) treatment, we demonstrated that oxidative stress is the primary element of damage in noise-induced cochlear injury and that increased inflammation can be considered a consequence of PPAR down-regulation induced by ROS production. Indeed, by decreasing oxidative stress, PPARs returned to control values, reactivating the negative control on inflammation in a feedback loop.

Highlights

To characterize cochlear damage induced by noise exposure, we examined outer hair cells (OHCs) and IHC survival in surface preparations of the organ of Corti
Our results show that 19 oxexpression in cochlear structures; (2) reduced expression of PPARs is associated with idative stress and a progressive increase in inflammatory markers (NF-κB and interleukin 1-β (IL-1β)) in noise-exposed cochleae; (3) blocking oxidative stress through an antioxidant treatment reestablishes basal PPAR levels in the cochlea, leading to decreased expression of the recochleae; (3) blocking oxidative stress through an antioxidant treatment reestablishes basal dox-sensitive transcription factortoof inflammation related genes
By Western blot and immunofluorescence analysis, we showed that PPARα and PPARγ cochlear expression was severely affected by noise exposure, with a progressive decrease in protein levels over time from day 1 to day 7 after acoustic trauma

Summary

Introduction

Recent findings in hearing loss research have provided strong evidence for common predominant mechanisms of damage affecting the organ of Corti: the unbalance of cellular redox status and inflammation. The noise-induced reactive oxygen species (ROS) interact in many ways with the key transcription factor driving inflammation, the nuclear factor kappa-B (NF-κB) signaling pathway [1,2,3,4]. Noise exposure has been shown to up-regulate cochlear production of cytokines [5,6,7], such as interleukin 1-β (IL-1β), that have been observed after ROS generation in the cochlea [8]. Similar mechanisms have been reported to occur in drug-induced hearing loss [9,10] and aging [11]

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