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

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1188
Author(s):  
Fabiola Paciello ◽  
Anna Pisani ◽  
Rolando Rolesi ◽  
Vincent Escarrat ◽  
Jacopo Galli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Negative Control ◽  
In Vivo Model ◽  
Noise Induced Hearing Loss ◽  
Down Regulation ◽  
Anti Inflammatory ◽  
Cochlear Dysfunction

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.

MicroRNAs in Noise-Induced Hearing Loss and their Regulation by Oxidative Stress and Inflammation

2020 ◽  
Vol 21 (12) ◽  
pp. 1216-1224
Author(s):  
Fatemeh Forouzanfar ◽  
Samira Asgharzade
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Hair Cell ◽  
Noise Exposure ◽  
Cell Damage ◽  
Sensory Cells ◽  
Noise Induced Hearing Loss ◽  
Irreversible Damage ◽  
Open Access Journals

Noise exposure (NE) has been recognized as one of the causes of sensorineural hearing loss (SNHL), which can bring about irreversible damage to sensory hair cells in the cochlea, through the launch of oxidative stress pathways and inflammation. Accordingly, determining the molecular mechanism involved in regulating hair cell apoptosis via NE is essential to prevent hair cell damage. However, the role of microRNAs (miRNAs) in the degeneration of sensory cells of the cochlea during NE has not been so far uncovered. Thus, the main purpose of this study was to demonstrate the regulatory role of miRNAs in the oxidative stress pathway and inflammation induced by NE. In this respect, articles related to noise-induced hearing loss (NIHL), oxidative stress, inflammation, and miRNA from various databases of Directory of Open Access Journals (DOAJ), Google Scholar, PubMed; Library, Information Science & Technology Abstracts (LISTA), and Web of Science were searched and retrieved. The findings revealed that several studies had suggested that up-regulation of miR-1229-5p, miR-451a, 185-5p, 186 and down-regulation of miRNA-96/182/183 and miR-30b were involved in oxidative stress and inflammation which could be used as biomarkers for NIHL. There was also a close relationship between NIHL and miRNAs, but further research is required to prove a causal association between miRNA alterations and NE, and also to determine miRNAs as biomarkers indicating responses to NE.

scholarly journals Primed to die: an investigation of the genetic mechanisms underlying noise-induced hearing loss and cochlear damage in homozygous Foxo3-knockout mice

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Holly J. Beaulac ◽  
Felicia Gilels ◽  
Jingyuan Zhang ◽  
Sarah Jeoung ◽  
Patricia M. White
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Multiphoton Microscopy ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Noise Induced Hearing Loss ◽  
Knock Out ◽  
Cell Death Pathway ◽  
Cochlear Damage

AbstractThe prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo3+/−), and Foxo3 knock-out (Foxo3−/−) mice to better understand FOXO3’s role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and caspase-independent apoptosis. Lower immunoreactivity of the calcium buffer Oncomodulin in Foxo3−/− OHCs correlated with cell loss beginning 4 h post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3’s absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposed Foxo3−/− mice that may contribute to OHC noise susceptibility. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea. As LPA reduces OHC loss after severe noise exposure, we treated noise-exposed Foxo3−/− mice with exogenous LPA. LPA treatment delayed immediate damage to OHCs but was insufficient to ultimately prevent their death or prevent hearing loss. These results suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, possibly through sustaining endogenous LPA levels.

scholarly journals Inhibition of Cochlear HMGB1 Expression Attenuates Oxidative Stress and Inflammation in an Experimental Murine Model of Noise-Induced Hearing Loss

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 810
Author(s):  
Cheng-Ping Shih ◽  
Chao-Yin Kuo ◽  
Yuan-Yung Lin ◽  
Yi-Chun Lin ◽  
Hang-Kang Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Outer Hair Cells ◽  
Control Group ◽  
Noise Induced Hearing Loss ◽  
Post Exposure ◽  
Nadph Oxidase 4 ◽  
Brainstem Response ◽  
Ros Formation

Noise-induced hearing loss (NIHL) is a common inner ear disease but has complex pathological mechanisms, one of which is increased oxidative stress in the cochlea. The high-mobility group box 1 (HMGB1) protein acts as an inflammatory mediator and shows different activities with redox modifications linked to the generation of reactive oxygen species (ROS). We aimed to investigate whether manipulation of cochlear HMGB1 during noise exposure could prevent noise-induced oxidative stress and hearing loss. Sixty CBA/CaJ mice were divided into two groups. An intraperitoneal injection of anti-HMGB1 antibodies was administered to the experimental group; the control group was injected with saline. Thirty minutes later, all mice were subjected to white noise exposure. Subsequent cochlear damage, including auditory threshold shifts, hair cell loss, expression of cochlear HMGB1, and free radical activity, was then evaluated. The levels of HMGB1 and 4-hydroxynonenal (4-HNE), as respective markers of reactive nitrogen species (RNS) and ROS formation, showed slight increases on post-exposure day 1 and achieved their highest levels on post-exposure day 4. After noise exposure, the antibody-treated mice showed markedly less ROS formation and lower expression of NADPH oxidase 4 (NOX4), nitrotyrosine, inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM‑1) than the saline-treated control mice. A significant amelioration was also observed in the threshold shifts of the auditory brainstem response and the loss of outer hair cells in the antibody-treated versus the saline-treated mice. Our results suggest that inhibition of HMGB1 by neutralization with anti-HMGB1 antibodies prior to noise exposure effectively attenuated oxidative stress and subsequent inflammation. This procedure could therefore have potential as a therapy for NIHL.

scholarly journals Primed to Die: An Investigation of the Genetic Mechanisms Underlying Noise-Induced Hearing Loss and Cochlear Damage in Homozygous Foxo3-knockout Mice

2021 ◽  
Author(s):  
Holly J. Beaulac ◽  
Felicia Gilels ◽  
Jingyuan Zhang ◽  
Sarah Jeoung ◽  
Patricia M. White
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Multiphoton Microscopy ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Noise Induced Hearing Loss ◽  
Knock Out ◽  
Cell Death Pathway ◽  
Cochlear Damage

AbstractThe prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following a mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo3+/KO), and Foxo3 knock-out (Foxo3KO/KO) mice to better understand FOXO3’s role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and -independent apoptosis. Lower immunoreactivity of the calcium buffer oncomodulin in Foxo3KO/KO OHCs correlated with cell loss beginning 4 hours post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3’s absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposed Foxo3KO/KO mice that may contribute to OHC noise susceptibility. Glycerophosphodiester Phosphodiesterase Domain Containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea. As LPA reduces OHC loss after severe noise exposure, we treated noise exposed Foxo3KO/KO mice with exogenous LPA. LPA treatment delayed immediate damage to OHCs but was insufficient to ultimately prevent their death or prevent hearing loss. These results suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, possibly through sustaining endogenous LPA levels.

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

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.

scholarly journals Anti-Inflammatory Effect of Allium ursinum

2014 ◽  
Vol 6 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Alina Elena PÂRVU ◽  
Florinela CĂTOI ◽  
Sameera DEELAWAR ◽  
Darshana SARUP ◽  
Marcel PÂRVU
Keyword(s):  
Oxidative Stress ◽  
Inhibitory Effect ◽  
Negative Control ◽  
Stress Index ◽  
Allium Ursinum ◽  
Total Oxidative Status ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The aim of the present study was to evaluate Allium ursinum leaves and flowers extract anti-inflammatory effect. Plant extract 1:1 (w:v) was prepared from A. ursinum leaves by a modified Squibb repercolation method. The in vivo anti-inflammatory effects were evaluated on a rat turpentine oil-induced inflammation (i.m. 6 mL/kg BW). The animals were randomly assigned to nine groups (n=8): negative control, inflammation, A. ursinum flower extract (AUF), A. ursinum leaves extract (AUL), indomethacin (INDO) (20 mg/kg BW), aminoguanidine (AG) (50 mg/kg b.w./d i.p.) as a selective NOS2 inhibitor, NG-nitro L-arginine methyl ester (NAME) (5 mg/kg b.w./d i.p.) as a nonselective NOS inhibitor, L-arginine (ARG) (100 mg/kg b.w./d i.p.), NO synthesis substrate, and Trolox (20 mg/kg b.w./d i.p) as an antioxidant. At 24h from inflammation induction total oxidative status (TOS), oxidative stress index (OSI), nitric oxide (NOx) and in vitro phagocytosis test were reduced and the total antioxidative reactivity (TAR) was increased by the testes plant extracts. AUF had a better inhibitory effect than AUL. In conclusion, we provided evidence for the hypothesis that A. ursinum leaves and flowers extract exerts anti-inflammatory activity by inhibiting the phagocytosis through the reduction of the nitro-oxidative stress.

Anti-oxidant and anti-inflammatory effects of caffeic acid: in vivo evidences in a model of noise-induced hearing loss

2020 ◽  
Vol 143 ◽  
pp. 111555
Author(s):  
Fabiola Paciello ◽  
Antonella Di Pino ◽  
Rolando Rolesi ◽  
Diana Troiani ◽  
Gaetano Paludetti ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Caffeic Acid ◽  
Noise Induced Hearing Loss ◽  
Anti Oxidant ◽  
Anti Inflammatory

Noise Exposure and Hearing Disorders

2017 ◽  
Author(s):  
David C. Byrne ◽  
Thais C. Morata
Keyword(s):  
Hearing Loss ◽  
Noise Exposure ◽  
Hearing Protection ◽  
Noise Induced Hearing Loss ◽  
Hearing Disorders ◽  
Industrial Noise ◽  
Significant Impairment ◽  
Protection Devices ◽  
The Impact ◽  
Occupational Hearing Loss

Exposure to industrial noise and the resulting effect of occupational hearing loss is a common problem in nearly all industries. This chapter describes industrial noise exposure, its assessment, and hearing disorders that result from overexposure to noise. Beginning with the properties of sound, noise-induced hearing loss and other effects of noise exposure are discussed. The impact of hearing disorders and the influence of other factors on hearing loss are described. Typically, noise-induced hearing loss develops slowly, and usually goes unnoticed until a significant impairment has occurred. Fortunately, occupational hearing loss is nearly always preventable. Therefore, this chapter gives particular attention to recommendations for measures to prevent occupational hearing loss such as engineering noise controls and hearing protection devices.

scholarly journals Contributions and limitations of using machine learning to predict noise-induced hearing loss

2021 ◽  
Author(s):  
Feifan Chen ◽  
Zuwei Cao ◽  
Emad M. Grais ◽  
Fei Zhao
Keyword(s):  
Machine Learning ◽  
Hearing Loss ◽  
Roc Curve ◽  
Prediction Error ◽  
Noise Exposure ◽  
Model Construction ◽  
Support Vector ◽  
Exposure Level ◽  
Noise Induced Hearing Loss ◽  
Current Review

Abstract Purpose Noise-induced hearing loss (NIHL) is a global issue that impacts people’s life and health. The current review aims to clarify the contributions and limitations of applying machine learning (ML) to predict NIHL by analyzing the performance of different ML techniques and the procedure of model construction. Methods The authors searched PubMed, EMBASE and Scopus on November 26, 2020. Results Eight studies were recruited in the current review following defined inclusion and exclusion criteria. Sample size in the selected studies ranged between 150 and 10,567. The most popular models were artificial neural networks (n = 4), random forests (n = 3) and support vector machines (n = 3). Features mostly correlated with NIHL and used in the models were: age (n = 6), duration of noise exposure (n = 5) and noise exposure level (n = 4). Five included studies used either split-sample validation (n = 3) or ten-fold cross-validation (n = 2). Assessment of accuracy ranged in value from 75.3% to 99% with a low prediction error/root-mean-square error in 3 studies. Only 2 studies measured discrimination risk using the receiver operating characteristic (ROC) curve and/or the area under ROC curve. Conclusion In spite of high accuracy and low prediction error of machine learning models, some improvement can be expected from larger sample sizes, multiple algorithm use, completed reports of model construction and the sufficient evaluation of calibration and discrimination risk.

scholarly journals Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 443
Author(s):  
Hyunjun Woo ◽  
Min-Kyung Kim ◽  
Sohyeon Park ◽  
Seung-Hee Han ◽  
Hyeon-Cheol Shin ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Noise Exposure ◽  
Radical Scavenging ◽  
Threshold Shift ◽  
Ecklonia Cava ◽  
Control Group ◽  
Noise Induced Hearing Loss ◽  
Antioxidant Agents ◽  
Brainstem Response

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

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