TNF-α inhibition using etanercept prevents noise-induced hearing loss by improvement of cochlear blood flow in vivo

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.

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TMT-Based Quantitative Proteomics Reveals Cochlear Protein Profile Alterations in Mice with Noise-Induced Hearing Loss

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph19010382 ◽

2021 ◽

Vol 19 (1) ◽

pp. 382

Author(s):

Long Miao ◽

Juan Zhang ◽

Lihong Yin ◽

Yuepu Pu

Keyword(s):

Hearing Loss ◽

Mouse Model ◽

Western Blotting ◽

Quantitative Proteomics ◽

Protein Profile ◽

Outer Hair Cells ◽

Receptor Interaction ◽

Noise Induced Hearing Loss ◽

Tandem Mass Tag ◽

Tnf Α

Noise-induced hearing loss (NIHL) is a global occupational disease affecting health. To date, genetic polymorphism studies on NIHL have been performed extensively. However, the proteomic profiles in the cochleae of mice suffering noise damage remain unclear. The goal of this current study was to perform a comprehensive investigation on characterizing protein expression changes in the cochlea based on a mouse model of NIHL using tandem mass tag (TMT)-labeling quantitative proteomics, and to reveal the potential biomarkers and pathogenesis of NIHL. Male C57BL/6J mice were exposed to noise at 120 dB SPL for 4 h to construct the NIHL mouse model. The levels of MDA and SOD, and the production of proinflammatory cytokines including TNF-α and IL-6 in the mice cochleae, were determined using chemical colorimetrical and ELISA kits. Moreover, differentially expressed proteins (DEPs) were validated using Western blotting. The mouse model showed that the ABR thresholds at frequencies of 4, 8, 12, 16, 24 and 32 kHz were significantly increased, and outer hair cells (HCs) showed a distinct loss in the noise-exposed mice. Proteomics analysis revealed that 221 DEPs were associated with NIHL. Bioinformatics analysis showed that a set of key inflammation and autophagy-related DEPs (ITGA1, KNG1, CFI, FGF1, AKT2 and ATG5) were enriched in PI3K/AKT, ECM-receptor interaction, and focal adhesion pathways. The results revealed that the MDA level was significantly increased, but the activity of SOD decreased in noise-exposed mice compared to the control mice. Moreover, TNF-α and IL-6 were significantly increased in the noise-exposed mice. Western blotting revealed that the expression levels of ITGA1, KNG1, and CFI were upregulated, but FGF1, AKT2, and ATG5 were significantly downregulated in noise-exposed mice. This study provides new scientific clues about the future biomarkers and pathogenesis studies underlying NIHL. Furthermore, the findings suggest that the validated DEPs may be valuable biomarkers of NIHL, and inflammation and autophagy may be pivotal mechanisms that underlie NIHL.

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Free Radical Damage and Noise-Induced Hearing Loss: in vivo in situ Sensing

10.21236/ada501567 ◽

2008 ◽

Author(s):

ILLINOIS UNIV CHAMPAIGN

Keyword(s):

Hearing Loss ◽

Free Radical ◽

Noise Induced Hearing Loss ◽

Free Radical Damage ◽

In Situ Sensing ◽

Radical Damage

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Recent Advances in Cochlear Blood Flow Measurements

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348948809700101 ◽

1988 ◽

Vol 97 (1) ◽

pp. 1-8 ◽

Cited By ~ 27

Author(s):

Jonathon S. Sillman ◽

Michael J. Larouere ◽

Alfred L. Nuttall ◽

Merle Lawrence ◽

Josef M. Miller

Keyword(s):

Blood Flow ◽

Hearing Loss ◽

Inner Ear ◽

Laser Doppler ◽

Control Mechanisms ◽

Clinical Value ◽

Cochlear Blood Flow ◽

Flow Measurements ◽

Local Flow ◽

Doppler Flowmetry

Changes in blood flow to the inner ear have been thought to influence or underlie a number of cochlear diseases, including some forms of noise-induced hearing loss, sudden hearing loss, and Meniere's disease. Recently, important advances have been made in two technologies for the study of cochlear blood flow. The first is in the area of vital microscopic studies of cochlear microcirculation, and the second is based on the introduction of laser technology in the form of laser Doppler flowmetry. In this report, measurements are given of changes in cochlear circulation caused by carbon dioxide breathing, intravenous phenylephrine injection, systemic hemodilution, positive end expiratory pressure, and direct electrical stimulation of the cochlea. From these changes, we observe that cochlear blood circulation responds to systemic blood pressure alterations and is subject to local flow control mechanisms. Linearity and speed of response of the laser Doppler instrumentation also are shown. These advances show promise for contributing to our knowledge of control mechanisms of inner ear blood flow and for revealing the influence of various pharmacologic agents of potential clinical value.

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Targeting Inflammatory Processes Mediated by TRPVI and TNF-α for Treating Noise-Induced Hearing Loss

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2019.00444 ◽

2019 ◽

Vol 13 ◽

Cited By ~ 4

Author(s):

Asmita Dhukhwa ◽

Puspanjali Bhatta ◽

Sandeep Sheth ◽

Krishi Korrapati ◽

Coral Tieu ◽

...

Keyword(s):

Hearing Loss ◽

Noise Induced Hearing Loss ◽

Tnf Α ◽

Inflammatory Processes

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A Contribution to the Physiology of the Perilymph Part III: On the Origin of Noise-Induced Hearing Loss

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348947408300319 ◽

1974 ◽

Vol 83 (3) ◽

pp. 406-412 ◽

Cited By ~ 13

Author(s):

Ernst-August Schnieder

Keyword(s):

Blood Flow ◽

Hearing Loss ◽

Exchange Rate ◽

White Noise ◽

Oxygen Supply ◽

Prolonged Exposure ◽

Organ Of Corti ◽

Sensory Cells ◽

Cochlear Blood Flow ◽

Critical Intensity

After exposure to white noise (SPL > 90 dB) the cochlear half life (τ) is increased by 100%. After exposure to white noise (90 dB<SPL<105 dB) the concentration of lactate in the perilymph increases significantly, while the blood level remains constant. Both results are capable of supporting the hypothesis that exposure to noise of a critical intensity (which appears to lie beween 90 and 100 dB) reduces cochlear blood flow. This reduction in turn diminishes the exchange rate of perilymph and reduces the oxygen supply to the sensory cells. The subsequent hypoxidosis of the organ of Corti may cause metabolic breakdown in, and on prolonged exposure, degeneration of the sensory cells. Both results are further capable of supporting the hypothesis outlined in Part I, that perilymph is the medium of transport to and from the cells of the organ of Corti.

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FBXO3 Downregulation Attenuates Noise-induced Hearing Loss by Suppressing ATG10 Degradation and Activating Autophagy

10.21203/rs.3.rs-120982/v1 ◽

2020 ◽

Author(s):

Fan Ye ◽

Bi Lin ◽

Lian Fang

Keyword(s):

Hearing Loss ◽

Noise Exposure ◽

Underlying Mechanism ◽

Noise Induced Hearing Loss ◽

Age Related ◽

Rat Cochlea ◽

Model Treatment ◽

Ear Injury ◽

Age Related Hearing Loss

Abstract Noise induced hearing loss (NIHL) is a kind of hearing impairment, which is next to the age-related hearing loss. More and more evidences have verified that overproduction of reactive oxygen species is a common pathologic phenomenon of different inner ear injury including NIHL, and autophagy contributes to attenuate NIHL by reducing oxidative stress. However, the underlying mechanism by which noise exposure causes autophagy activation remains unclear. In this study, we found that NIHL was accompanied by autophagy in the rat cochlea. Furthermore, twelve common genes were found at the GEO datasets GSE85290 and GSE8342, and E3 ubiquitination ligase FBXO3 was confirmed significantly reduced in NIHL rat cochlea. Next, we demonstrated that FBXO3 can directly binding with autophagy-related protein 10 (ATG10), which is necessary for the initiation of autophagy, and mediate its degradation. In vivo animal model treatment with rapamycin, an autophagy activator, significantly reduced the NIHL. Based on these data, we confirmed that FBXO3 played an important role in autophagy caused by NIHL, may be a potential target of NIHL treatment.

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