scholarly journals Role of Oxidative Stress in the Senescence Pattern of Auditory Cells in Age-Related Hearing Loss

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1497
Author(s):  
Luz del Mar Rivas-Chacón ◽  
Sofía Martínez-Rodríguez ◽  
Raquel Madrid-García ◽  
Joaquín Yanes-Díaz ◽  
Juan Ignacio Riestra-Ayora ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Cell Damage ◽  
Stria Vascularis ◽  
Organ Of Corti ◽  
Age Related ◽  
Age Related Hearing Loss

Age-related hearing loss (ARHL) is an increasing and gradual sensorineural hearing dysfunction. Oxidative stress is an essential factor in developing ARHL; additionally, premature senescence of auditory cells induced by oxidative stress can produce hearing loss. Hydrogen peroxide (H2O2) represents a method commonly used to generate cellular senescence in vitro. The objective of the present paper is to study H2O2-induced senescence patterns in three auditory cell lines (House Ear Institute-Organ of Corti 1, HEI-OC1; organ of Corti, OC-k3, and stria vascularis, SV-k1 cells) to elucidate the intrinsic mechanisms responsible for ARHL. The auditory cells were exposed to H2O2 at different concentrations and times. The results obtained show different responses of the hearing cells concerning cell growth, β-galactosidase activity, morphological changes, mitochondrial activation, levels of oxidative stress, and other markers of cell damage (Forkhead box O3a, FoxO3a, and 8-oxoguanine, 8-oxoG). Comparison between the responses of these auditory cells to H2O2 is a helpful method to evaluate the molecular mechanisms responsible for these auditory cells’ senescence. Furthermore, this in vitro model could help develop anti-senescent therapeutic strategies for the treatment of AHRL.

scholarly journals Prediction of the Molecular Mechanisms Underlying Erlong Zuoci Treatment of Age-Related Hearing Loss via Network Pharmacology-Based Analyses Combined with Experimental Validation

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Liu ◽  
Ning Li ◽  
Yifang Yang ◽  
Xirui Yan ◽  
Yang Dong ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Experimental Validation ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Synaptic Connections ◽  
Target Proteins ◽  
Age Related ◽  
Age Related Hearing Loss

Background: The traditional Chinese medicine formula ErLong ZuoCi (ELZC) has been extensively used to treat age-related hearing loss (ARHL) in clinical practice in China for centuries. However, the underlying molecular mechanisms are still poorly understood.Objective: Combine network pharmacology with experimental validation to explore the potential molecular mechanisms underlying ELZC with a systematic viewpoint.Methods: The chemical components of ELZC were collected from the Traditional Chinese Medicine System Pharmacology database, and their possible target proteins were predicted using the SwissTargetPrediction database. The putative ARHL-related target proteins were identified from the database: GeneCards and OMIM. We constructed the drug-target network as well as drug-disease specific protein-protein interaction networks and performed clustering and topological property analyses. Functional annotation and signaling pathways were performed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Finally, in vitro experiments were also performed to validate ELZC’s key target proteins and treatment effects on ARHL.Results: In total, 63 chemical compounds from ELZC and 365 putative ARHL-related targets were identified, and 1860 ARHL-related targets were collected from the OMIM and GeneCards. A total of 145 shared targets of ELZC and ARHL were acquired by Venn diagram analysis. Functional enrichment analysis suggested that ELZC might exert its pharmacological effects in multiple biological processes, such as cell proliferation, apoptosis, inflammatory response, and synaptic connections, and the potential targets might be associated with AKT, ERK, and STAT3, as well as other proteins. In vitro experiments revealed that ELZC pretreatment could decrease senescence-associated β-galactosidase activity in hydrogen peroxide-induced auditory hair cells, eliminate DNA damage, and reduce cellular senescence protein p21 and p53. Finally, Western blot analysis confirmed that ELZC could upregulate the predicted target ERK phosphorylation.Conclusion: We provide an integrative network pharmacology approach, in combination with in vitro experiments to explore the underlying molecular mechanisms governing ELZC treatment of ARHL. The protective effects of ELZC against ARHL were predicted to be associated with cellular senescence, inflammatory response, and synaptic connections which might be linked to various pathways such as JNK/STAT3 and ERK cascade signaling pathways. As a prosperous possibility, our experimental data suggest phosphorylation ERK is essential for ELZC to prevent degeneration of cochlear.

scholarly journals Oxidative Stresses and Mitochondrial Dysfunction in Age-Related Hearing Loss

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Chisato Fujimoto ◽  
Tatsuya Yamasoba
Keyword(s):  
Hearing Loss ◽  
Mitochondrial Dysfunction ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
The Elderly ◽  
Laboratory Animals ◽  
Age Related ◽  
Ganglion Neurons ◽  
Age Related Hearing Loss

Age-related hearing loss (ARHL), the progressive loss of hearing associated with aging, is the most common sensory disorder in the elderly population. The pathology of ARHL includes the hair cells of the organ of Corti, stria vascularis, and afferent spiral ganglion neurons as well as the central auditory pathways. Many studies have suggested that the accumulation of mitochondrial DNA damage, the production of reactive oxygen species, and decreased antioxidant function are associated with subsequent cochlear senescence in response to aging stress. Mitochondria play a crucial role in the induction of intrinsic apoptosis in cochlear cells. ARHL can be prevented in laboratory animals by certain interventions, such as caloric restriction and supplementation with antioxidants. In this review, we will focus on previous research concerning the role of the oxidative stress and mitochondrial dysfunction in the pathology of ARHL in both animal models and humans and introduce concepts that have recently emerged regarding the mechanisms of the development of ARHL.

scholarly journals A Review on Recent Advancement on Age-Related Hearing Loss: The Applications of Nanotechnology, Drug Pharmacology, and Biotechnology

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1041
Author(s):  
Jacqueline Chester ◽  
Edan Johnston ◽  
Daniel Walker ◽  
Melissa Jones ◽  
Corina Mihaela Ionescu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Bile Acid ◽  
Hearing Aids ◽  
Stria Vascularis ◽  
Cellular Damage ◽  
Relevant Evidence ◽  
Neuronal Signalling ◽  
Age Related ◽  
Recent Advancement ◽  
Age Related Hearing Loss

Aging is considered a contributing factor to many diseases such as cardiovascular disease, Alzheimer’s disease, and hearing loss. Age-related hearing loss, also termed presbycusis, is one of the most common sensory impairments worldwide, affecting one in five people over 50 years of age, and this prevalence is growing annually. Associations have emerged between presbycusis and detrimental health outcomes, including social isolation and mental health. It remains largely untreatable apart from hearing aids, and with no globally established prevention strategies in the clinical setting. Hence, this review aims to explore the pathophysiology of presbycusis and potential therapies, based on a recent advancement in bile acid-based bio-nanotechnologies. A comprehensive online search was carried out using the following keywords: presbycusis, drugs, hearing loss, bile acids, nanotechnology, and more than 150 publications were considered directly relevant. Evidence of the multifaceted oxidative stress and chronic inflammation involvement in cellular damage and apoptosis that is associated with a loss of hair cells, damaged and inflamed stria vascularis, and neuronal signalling loss and apoptosis continues to emerge. New robust and effective therapies require drug delivery deeper into the various layers of the cochlea. Bile acid-based nanotechnology has gained wide interest in its permeation-enhancing ability and potential for numerous applications in treating presbycusis.

scholarly journals Multiphoton NAD(P)H FLIM reveals metabolic changes in individual cell types of the intact cochlea upon sensorineural hearing loss

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Paromita Majumder ◽  
Thomas S. Blacker ◽  
Lisa S. Nolan ◽  
Michael R. Duchen ◽  
Jonathan E. Gale
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Cell Model ◽  
Organ Of Corti ◽  
Cell Types ◽  
Fluorescence Lifetime Imaging ◽  
Noise Induced Hearing Loss ◽  
Label Free ◽  
Age Related ◽  
The Individual

AbstractAn increasing volume of data suggests that changes in cellular metabolism have a major impact on the health of tissues and organs, including in the auditory system where metabolic alterations are implicated in both age-related and noise-induced hearing loss. However, the difficulty of access and the complex cyto-architecture of the organ of Corti has made interrogating the individual metabolic states of the diverse cell types present a major challenge. Multiphoton fluorescence lifetime imaging microscopy (FLIM) allows label-free measurements of the biochemical status of the intrinsically fluorescent metabolic cofactors NADH and NADPH with subcellular spatial resolution. However, the interpretation of NAD(P)H FLIM measurements in terms of the metabolic state of the sample are not completely understood. We have used this technique to explore changes in metabolism associated with hearing onset and with acquired (age-related and noise-induced) hearing loss. We show that these conditions are associated with altered NAD(P)H fluorescence lifetimes, use a simple cell model to confirm an inverse relationship between τbound and oxidative stress, and propose such changes as a potential index of oxidative stress applicable to all mammalian cell types.

scholarly journals A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress

2017 ◽  
Author(s):  
Nicola J. Drummond ◽  
Nick O. Davies ◽  
Janet E. Lovett ◽  
Mark R. Miller ◽  
Graeme Cook ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Damage ◽  
Radical Scavenging ◽  
Head Group ◽  
Neural Cells ◽  
Zebrafish Model ◽  
Free System ◽  
Age Related

AbstractExcessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson’s disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and mitochondrial localisation of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against oxidative stress in a zebrafish model of dopaminergic neuronal loss.

scholarly journals Hearing Disorders and Sensorineural Aging

2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Alessandra Fioretti ◽  
Otello Poli ◽  
Theodoros Varakliotis ◽  
Alberto Eibenstein
Keyword(s):  
Hearing Loss ◽  
Organ Of Corti ◽  
Physiological Age ◽  
Hearing Disorders ◽  
Hearing Sensitivity ◽  
Age Related ◽  
Loss Of Autonomy ◽  
Central Auditory Function ◽  
Central Auditory Pathways ◽  
Age Related Hearing Loss

The physiological age-related hearing loss is defined as presbycusis and it is characterized by reduced hearing sensitivity and problems in understanding spoken language especially in a noisy environment. In elderly the reduced speech recognition is generally caused by a reduction of the cochlear cells in the organ of Corti and degeneration of the central auditory pathways. In order to have a complete management strategy of central and peripheral presbycusis the diagnostic evaluation should include clinical ENT examination, standard audiological tests, and tests of central auditory function. Treatment should include not only the appropriate instruments for peripheral compensation but also auditory rehabilitative training and counseling to prevent social isolation and loss of autonomy. Other common hearing disorders in elderly are tinnitus and hyperacusis which are often undervalued. Tinnitus is characterized by the perception of a “phantom” sound due to abnormal auditory perception. Hyperacusis is defined as a reduced tolerance to ordinary environmental sounds. Furthermore auditory, visual, nociceptive, and proprioceptive systems may be involved together in a possible context of “sensorineural aging.” The aim of this review is to underline the presence of hearing disorders like tinnitus and hyperacusis which in many cases coexist with hearing loss in elderly.

scholarly journals Mitochondria-Targeted Antioxidants for Treatment of Hearing Loss: A Systematic Review

Antioxidants ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 109 ◽  
Author(s):  
Chisato Fujimoto ◽  
Tatsuya Yamasoba
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Mitochondrial Dysfunction ◽  
Cell Lines ◽  
Mitochondrial Gene ◽  
Protective Effects ◽  
Drug Induced ◽  
Age Related ◽  
Cochlear Damage ◽  
Age Related Hearing Loss

Mitochondrial dysfunction is associated with the etiologies of sensorineural hearing loss, such as age-related hearing loss, noise- and ototoxic drug-induced hearing loss, as well as hearing loss due to mitochondrial gene mutation. Mitochondria are the main sources of reactive oxygen species (ROS) and ROS-induced oxidative stress is involved in cochlear damage. Moreover, the release of ROS causes further damage to mitochondrial components. Antioxidants are thought to counteract the deleterious effects of ROS and thus, may be effective for the treatment of oxidative stress-related diseases. The administration of mitochondria-targeted antioxidants is one of the drug delivery systems targeted to mitochondria. Mitochondria-targeted antioxidants are expected to help in the prevention and/or treatment of diseases associated with mitochondrial dysfunction. Of the various mitochondria-targeted antioxidants, the protective effects of MitoQ and SkQR1 against ototoxicity have been previously evaluated in animal models and/or mouse auditory cell lines. MitoQ protects against both gentamicin- and cisplatin-induced ototoxicity. SkQR1 also provides auditory protective effects against gentamicin-induced ototoxicity. On the other hand, decreasing effect of MitoQ on gentamicin-induced cell apoptosis in auditory cell lines has been controversial. No clinical studies have been reported for otoprotection using mitochondrial-targeted antioxidants. High-quality clinical trials are required to reveal the therapeutic effect of mitochondria-targeted antioxidants in terms of otoprotection in patients.

Molecular mechanisms of age-related hearing loss

2002 ◽  
Vol 1 (3) ◽  
pp. 331-343 ◽  
Author(s):  
Michael D. Seidman ◽  
Nadir Ahmad ◽  
Uma Bai
Keyword(s):  
Hearing Loss ◽  
Molecular Mechanisms ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-24 ◽  
Author(s):  
Mika Reinisalo ◽  
Anna Kårlund ◽  
Ali Koskela ◽  
Kai Kaarniranta ◽  
Reijo O. Karjalainen
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cell Damage ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Age Related ◽  
Cellular Defence ◽  
The Impact ◽  
Stilbene Compounds

Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD), and Alzheimer’s disease (AD). In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer bark waste, may confer a protective effect against aging-related diseases. This review highlights recent data helping to clarify the molecular mechanisms involved in the stilbene-mediated protection against oxidative stress. The impact of stilbenes on the nuclear factor-erythroid-2-related factor-2 (Nrf2) mediated cellular defence against oxidative stress as well as the potential roles of SQSTM1/p62 protein in Nrf2/Keap1 signaling and autophagy will be summarized. The therapeutic potential of stilbene compounds against the most common aging-related diseases is discussed.

Physiological and Neurobiological Bases of Age-Related Hearing Loss: Biotherapeutic Implications

2013 ◽  
Vol 22 (2) ◽  
pp. 299-302 ◽  
Author(s):  
Robert D. Frisina ◽  
D. Robert Frisina
Keyword(s):  
Hearing Loss ◽  
Auditory Processing ◽  
Stria Vascularis ◽  
Positive Influence ◽  
Negative Effects ◽  
Age Related ◽  
Women And Aging ◽  
Auditory Tasks ◽  
And Function ◽  
Age Related Hearing Loss

Purpose The aim of this study was to highlight growing evidence of interactions between hormones and the structure and function of the auditory system. Method Recent studies implicating sex hormones and other natural hormones in the modulation of hearing status in age-related hearing loss were reviewed. Results Progesterone, a sex hormone, has been shown to have negative effects on the hearing of older women and aging mice, whereas, in contrast, estrogen was found in some cases to have a positive influence. Aldosterone, used in studies of animal models of autoimmune hearing loss, slowed the progression of hearing loss. Follow-up studies in humans revealed that auditory measures varied as serum aldosterone levels shifted within the normal range, in otherwise healthy older subjects. This was true for simple as well as complex auditory tasks (i.e., sound spatial processing), suggesting benefits of aldosterone to postperipheral auditory processing as well. In addition, evidence suggests that this functional hearing improvement occurred in association with anatomical improvements to the stria vascularis—an important site of anatomical change in presbycusis. Conclusions Audiology is now at the point where the search for biomedical interventions to modulate or prevent age-related hearing loss can move forward. Such interventions would require multidisciplinary collaborative initiatives by researchers in such areas as drug development, anatomy, auditory physiological and perceptual testing, and drug microdelivery systems.

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