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Antioxidants
Special Issues
Oxidative Stress in Hearing Loss
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Oxidative Stress in Hearing Loss

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: 28 February 2025 | Viewed by 9602

Special Issue Editors

Dr. Lei Song

E-Mail Website
Guest Editor
School of Medicine, Yale University, New Haven, CT, USA
Interests: ear; outer hair cell; inner ear
Prof. Dr. Joseph Santos-Sacchi

E-Mail Website
Guest Editor
School of Medicine, Yale University, New Haven, CT, USA
Interests: hair cells; auditory; ear; inner; neurosciences; otolaryngology; physiology

Special Issue Information

Dear Colleagues,

The topics of this Special Issue are oxidative stress and hearing loss. As we all know, increased oxidative stress in the inner ear is one of the most dominant etiologies of genetical or environmental hearing loss. In the last two decades or so, hearing loss caused by oxidative stress has continued to be a prominent topic in hearing research, involving both basic research and clinical applications. As most of the research articles are spread out in various journals, this Special Issue will collate the efforts of our colleagues. We hope this Special Issue will lead to strong research on this topic. 

Our objective is to invite authors from multidiscipline research fields to submit relevant research papers and reviews.

Dr. Lei Song
Prof. Dr. Joseph Santos-Sacchi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ear
  • outer hair cell
  • inner ear

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Published Papers (5 papers)

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Research

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20 pages, 8203 KiB  
Article
An In Vitro Oxidative Stress Model of the Human Inner Ear Using Human-Induced Pluripotent Stem Cell-Derived Otic Progenitor Cells
by Minjin Jeong, Sho Kurihara and Konstantina M. Stankovic
Antioxidants 2024, 13(11), 1407; https://doi.org/10.3390/antiox13111407 - 16 Nov 2024
Viewed by 426
Abstract
The inner ear organs responsible for hearing (cochlea) and balance (vestibular system) are susceptible to oxidative stress due to the high metabolic demands of their sensorineural cells. Oxidative stress-induced damage to these cells can cause hearing loss or vestibular dysfunction, yet the precise [...] Read more.
The inner ear organs responsible for hearing (cochlea) and balance (vestibular system) are susceptible to oxidative stress due to the high metabolic demands of their sensorineural cells. Oxidative stress-induced damage to these cells can cause hearing loss or vestibular dysfunction, yet the precise mechanisms remain unclear due to the limitations of animal models and challenges of obtaining living human inner ear tissue. Therefore, we developed an in vitro oxidative stress model of the pre-natal human inner ear using otic progenitor cells (OPCs) derived from human-induced pluripotent stem cells (hiPSCs). OPCs, hiPSCs, and HeLa cells were exposed to hydrogen peroxide or ototoxic drugs (gentamicin and cisplatin) that induce oxidative stress to evaluate subsequent cell viability, cell death, reactive oxygen species (ROS) production, mitochondrial activity, and apoptosis (caspase 3/7 activity). Dose-dependent reductions in OPC cell viability were observed post-exposure, demonstrating their vulnerability to oxidative stress. Notably, gentamicin exposure induced ROS production and cell death in OPCs, but not hiPSCs or HeLa cells. This OPC-based human model effectively simulates oxidative stress conditions in the human inner ear and may be useful for modeling the impact of ototoxicity during early pregnancy or evaluating therapies to prevent cytotoxicity. Full article
(This article belongs to the Special Issue Oxidative Stress in Hearing Loss)
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23 pages, 24222 KiB  
Article
Nuciferine Protects Cochlear Hair Cells from Ferroptosis through Inhibiting NCOA4-Mediated Ferritinophagy
by Xian Gao, Huanyu Mao, Liping Zhao, Xiang Li, Yaqi Liao, Wenyan Li, Huawei Li and Yan Chen
Antioxidants 2024, 13(6), 714; https://doi.org/10.3390/antiox13060714 - 12 Jun 2024
Cited by 1 | Viewed by 3747
Abstract
Cisplatin is a widely used antineoplastic drug for treating various types of cancers. However, it can cause severe side effects, such as bilateral and irreversible hearing loss, which significantly impacts quality of life. Ferroptosis, an iron-dependent form of programmed cell death, has been [...] Read more.
Cisplatin is a widely used antineoplastic drug for treating various types of cancers. However, it can cause severe side effects, such as bilateral and irreversible hearing loss, which significantly impacts quality of life. Ferroptosis, an iron-dependent form of programmed cell death, has been implicated in the pathogenesis of cisplatin-induced ototoxicity. Here, we investigated the effects of nuciferine, a natural active ingredient isolated from lotus species, on the ferroptosis of cochlear hair cells. Firstly, our results demonstrated that nuciferine can protect hair cells against RSL3-induced and cisplatin-induced damage. Secondly, nuciferine treatment reduced ferrous iron (Fe2+) overload in cochlear hair cells via inhibiting NCOA4-mediated ferritinophagy. Inhibition of ferritinophagy by knocking down Ncoa4 alleviated cisplatin-induced ototoxicity. Importantly, nuciferine treatment mitigated cochlear hair cell loss and damage to ribbon synapse, and improved mouse hearing function in an acute cisplatin-induced hearing loss model. Our findings highlight the role of NCOA4-mediated ferritinophagy in the pathogenesis of cisplatin-induced ototoxicity and provide evidence for nuciferine as a promising protective agent for treating cisplatin-induced hearing loss. Full article
(This article belongs to the Special Issue Oxidative Stress in Hearing Loss)
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14 pages, 3993 KiB  
Article
Lercanidipine’s Antioxidative Effect Prevents Noise-Induced Hearing Loss
by Zhaoqi Guo, E Tian, Sen Chen, Jun Wang, Jingyu Chen, Weijia Kong, Debbie C. Crans, Yisheng Lu and Sulin Zhang
Antioxidants 2024, 13(3), 327; https://doi.org/10.3390/antiox13030327 - 7 Mar 2024
Cited by 1 | Viewed by 1644
Abstract
Noise-induced hearing loss (NIHL) is a prevalent form of adult hearing impairment, characterized by oxidative damage to auditory sensory hair cells. Although certain dihydropyridines, the L-type calcium channel blockers, exhibit protective properties against such damage, the ability of third-generation dihydropryidines like lercanidipine to [...] Read more.
Noise-induced hearing loss (NIHL) is a prevalent form of adult hearing impairment, characterized by oxidative damage to auditory sensory hair cells. Although certain dihydropyridines, the L-type calcium channel blockers, exhibit protective properties against such damage, the ability of third-generation dihydropryidines like lercanidipine to mitigate NIHL remains unclear.We utilized glucose oxidase (GO)-treated OC1 cell lines and cochlear explants to evaluate the protective influence of lercanidipine on hair cells. To further investigate its effectiveness, we exposed noise-stimulated mice in vivo and analyzed their hearing thresholds. Additionally, we assessed the antioxidative capabilities of lercanidipine by examining oxidation-related enzyme expression and levels of oxidative stress markers, including 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE). Our findings demonstrate that lercanidipine significantly reduces the adverse impacts of GO on both OC-1 cell viability (0.3 to 2.5 µM) and outer hair cell (OHC) survival in basal turn cochlear explants (7 µM). These results are associated with increased mRNA expression of antioxidant enzyme genes (HO-1, SOD1/2, and Txnrd1), along with decreased expression of oxidase genes (COX-2, iNOS). Crucially, lercanidipine administration prior to, and following, noise exposure effectively ameliorates NIHL, as evidenced by lowered hearing thresholds and preserved OHC populations in the basal turn, 14 days post-noise stimulation at 110 dB SPL. Moreover, our observations indicate that lercanidipine’s antioxidative action persists even three days after simultaneous drug and noise treatments, based on 3-nitrotyrosine and 4-hydroxynonenal immunostaining in the basal turn. Based on these findings, we propose that lercanidipine has the capacity to alleviate NIHL and safeguard OHC survival in the basal turn, potentially via its antioxidative mechanism. These results suggest that lercanidipine holds promise as a clinically viable option for preventing NIHL in affected individuals. Full article
(This article belongs to the Special Issue Oxidative Stress in Hearing Loss)
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Review

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18 pages, 1437 KiB  
Review
Hearing Loss and Oxidative Stress: A Comprehensive Review
by A. Maniaci, L. La Via, J. R. Lechien, G. Sangiorgio, G. Iannella, G. Magliulo, A. Pace, Q. Mat, S. Lavalle and M. Lentini
Antioxidants 2024, 13(7), 842; https://doi.org/10.3390/antiox13070842 - 14 Jul 2024
Cited by 1 | Viewed by 1819
Abstract
Hearing loss is a prevalent condition affecting millions of people worldwide. Hearing loss has been linked to oxidative stress as a major factor in its onset and progression. The goal of this thorough analysis is to investigate the connection between oxidative stress and [...] Read more.
Hearing loss is a prevalent condition affecting millions of people worldwide. Hearing loss has been linked to oxidative stress as a major factor in its onset and progression. The goal of this thorough analysis is to investigate the connection between oxidative stress and hearing loss, with an emphasis on the underlying mechanisms and possible treatments. The review addressed the many forms of hearing loss, the role of reactive oxygen species (ROS) in causing damage to the cochlea, and the auditory system’s antioxidant defensive mechanisms. The review also goes over the available data that support the use of antioxidants and other methods to lessen hearing loss brought on by oxidative stress. We found that oxidative stress is implicated in multiple types of hearing loss, including age-related, noise-induced, and ototoxic hearing impairment. The cochlea’s unique anatomical and physiological characteristics, such as high metabolic activity and limited blood supply, make it particularly susceptible to oxidative damage. Antioxidant therapies have shown promising results in both animal models and clinical studies for preventing and mitigating hearing loss. Emerging therapeutic approaches, including targeted drug delivery systems and gene therapy, offer new possibilities for addressing oxidative stress in the auditory system. The significance of this review lies in its comprehensive analysis of the intricate relationship between oxidative stress and hearing loss. By synthesizing current knowledge and identifying gaps in understanding, this review provides valuable insights for both researchers and clinicians. It highlights the potential of antioxidant-based interventions and emphasizes the need for further research into personalized treatment strategies. Our findings on oxidative stress mechanisms may also affect clinical practice and future research directions. This review serves as a foundation for developing novel therapeutic approaches and may inform evidence-based strategies for the prevention and treatment of hearing loss, ultimately contributing to improved quality of life for millions affected by this condition worldwide. Full article
(This article belongs to the Special Issue Oxidative Stress in Hearing Loss)
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Other

Jump to: Research, Review

30 pages, 1339 KiB  
Systematic Review
Pathogenesis and New Pharmacological Approaches to Noise-Induced Hearing Loss: A Systematic Review
by Francisco Javier Santaolalla Sanchez, Juan David Gutierrez Posso, Francisco Santaolalla Montoya, Javier Aitor Zabala, Ane Arrizabalaga-Iriondo, Miren Revuelta and Ana Sánchez del Rey
Antioxidants 2024, 13(9), 1105; https://doi.org/10.3390/antiox13091105 - 12 Sep 2024
Viewed by 1167
Abstract
Noise-induced hearing loss (NIHL) is responsible for significant adverse effects on cognition, quality of life and work, social relationships, motor skills, and other psychological aspects. The severity of NIHL depends on individual patient characteristics, sound intensity, and mainly the duration of sound exposure. [...] Read more.
Noise-induced hearing loss (NIHL) is responsible for significant adverse effects on cognition, quality of life and work, social relationships, motor skills, and other psychological aspects. The severity of NIHL depends on individual patient characteristics, sound intensity, and mainly the duration of sound exposure. NIHL leads to the production of a reactive oxygen (ROS) inflammatory response and the activation of apoptotic pathways, DNA fragmentation, and cell death. In this situation, antioxidants can interact with free radicals as well as anti-apoptotics or anti-inflammatory substances and stop the reaction before vital molecules are damaged. Therefore, the aim of this study was to analyze the effects of different pharmacological treatments, focusing on exogenous antioxidants, anti-inflammatories, and anti-apoptotics to reduce the cellular damage caused by acoustic trauma in the inner ear. Experimental animal studies using these molecules have shown that they protect hair cells and reduce hearing loss due to acoustic trauma. However, there is a need for more conclusive evidence demonstrating the protective effects of antioxidant/anti-inflammatory or anti-apoptotic drugs’ administration, the timeline in which they exert their pharmacological action, and the dose in which they should be used in order to consider them as therapeutic drugs. Further studies are needed to fully understand the potential of these drugs as they may be a promising option to prevent and treat noise-induced hearing loss. Full article
(This article belongs to the Special Issue Oxidative Stress in Hearing Loss)
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