Search Results (148)

The effects of music exposure on vocal performers remain relatively unknown. This study aimed to assess the immediate and long-term effects of music and singing practice on the peripheral auditory system of vocal performers using otoscopy, pure-tone audiometry, and noise dosimetry. The hearing status, sound pressure levels (SPLs), and sound doses of 12 vocal performers with normal hearing at the study’s onset were evaluated. Pre- and post-study questionnaires regarding the participants’ otologic health and music-making activities, as well as repeated hearing evaluations, were implemented. Additionally, noise dosimetry was conducted on each participant’s most vocally active day of the week. Audiometric assessments generally revealed normal hearing thresholds, with some exceptions. Half of the participants exhibited elevated low-frequency thresholds and over half of the participants displayed emerging audiometric “notches” at 6000 Hz. Noise dosimetry measurements indicated that most of the participants were consistently exposed to SPLs during music-making activities that exceeded recommended limits. Questionnaire responses highlighted that the participants often engaged in extra-curricular music-making activities, frequently with piano accompaniment, and with little to no use of hearing protection devices. A few of the participants reported histories of otologic issues and potential hearing problems. Full article

Occupational exposure to carcinogenic respirable crystalline silica and noise requires a deeper understanding and an assessment of the possible health risks caused by their combined action. Data on individual exposure to respirable crystalline silica (RCS) and occupational noise (ON) was collected among 44 open-pit miners. The study group was divided into two groups according to the job tasks performed. The individual exposure, exceeding of maximum admissible concentration/intensity, and predicted hearing thresholds (HTs) (according to ISO 1999:2013) were compared between the groups directly participating in the technological process (group 1; N = 23) and performing auxiliary, supervising, or laboratory activities (group 2; N = 21). All the analysed indices were significantly higher for group 1; therefore, the job category may predict ON and RCS exposure among open-pit miners. A statistically significant relationship (r_s = 0.66, p < 0.05) was found between the time-weighted average (TWA) 8 h RCS and individual daily noise exposure levels. Exposure to noise in the course of employment causes the risk of hearing impairment (mean HTs for 2, 3, and 4 kHz > 25 dB) up to 74% and 4.4% (in the case of groups 1 and 2, respectively). Further studies are needed before conclusions concerning the effects of co-exposure to ON and RCS on open-pit miners can be made. Full article

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

Background: It has been reported in many previous studies that the lack of auditory input due to hearing loss (HL) can induce changes in the brain. However, most of these studies have focused on individuals with pre-lingual HL and have predominantly compared the characteristics of those with normal hearing (NH) to cochlear implant (CI) users in children. This study examined the visual and auditory evoked potential characteristics in NH listeners, individuals with bilateral HL, and CI users, including those with single-sided deafness. Methods: A total of sixteen participants (seven NH listeners, four individuals with bilateral sensorineural HL, and five CI users) completed speech testing in quiet and noise and evoked potential testing. For speech testing, the Korean version of the Hearing in Noise Test was used to assess individuals’ speech understanding ability in quiet and in noise (noise from the front, +90 degrees, and −90 degrees). For evoked potential testing, visual and auditory (1000 Hz, /ba/, and /da/) evoked potentials were measured. Results: The results showed that CI users understood speech better than those with HL in all conditions except for the noise from +90 and −90 degrees. In the CI group, a decrease in P1 amplitudes was noted across all channels after implantation. The NH group exhibited the highest amplitudes, followed by the HL group, with the CI group (post-CI) showing the lowest amplitudes. In terms of auditory evoked potentials, the smallest amplitude was observed in the pre-CI condition regardless of the type of stimulus. Conclusions: To the best of our knowledge, this is the first study that examined visual and auditory evoked potentials based on various hearing profiles. The characteristics of evoked potentials varied across participant groups, and further studies with CI users are necessary, as there are significant challenges in collecting and analyzing evoked potentials due to artifact issues on the CI side. Full article

Sensorineural hearing loss (SNHL), characterized by damage to the inner ear or auditory nerve, is a prevalent auditory disorder. This study explores the potential of Castanopsis echinocarpa (CAE) as a therapeutic agent for SNHL. In vivo experiments were conducted using zebrafish and mouse models. Zebrafish with neomycin-induced ototoxicity were treated with CAE, resulting in otic hair cell protection with an EC₅₀ of 0.49 µg/mL and a therapeutic index of 1020. CAE treatment improved auditory function and protected cochlear sensory cells in a mouse model after noise-induced hearing loss (NIHL). RNA sequencing of NIHL mouse cochleae revealed that CAE up-regulates genes involved in neurotransmitter synthesis, secretion, transport, and neuronal survival. Real-time qPCR validation showed that NIHL decreased the mRNA expression of genes related to neuronal function, such as Gabra1, Gad1, Slc32a1, CaMK2b, CaMKIV, and Slc17a7, while the CAE treatment significantly elevated these levels. In conclusion, our findings provide strong evidence that CAE protects against hearing loss by promoting sensory cell protection and enhancing the expression of genes critical for neuronal function and survival. Full article

Hearing loss is a health crisis that affects more than 60 million Americans. Currently, sodium thiosulfate is the only drug approved by the Food and Drug Administration (FDA) to counter hearing loss. Sirtuins were proposed as therapeutic targets in the search for new compounds or drugs to prevent or cure age-, noise-, or drug-induced hearing loss. Sirtuins are proteins involved in metabolic regulation with the potential to ameliorate sensorineural hearing loss. The mammalian sirtuin family includes seven members, SIRT1-7. This paper is a literature review on the sirtuins and their protective roles in sensorineural hearing loss. Literature search on the NCBI PubMed database and NUsearch included the keywords ‘sirtuin’ and ‘hearing’. Studies on sirtuins without relevance to hearing and studies on hearing without relevance to sirtuins were excluded. Only primary research articles with data on sirtuin expression and physiologic auditory tests were considered. The literature review identified 183 records on sirtuins and hearing. After removing duplicates, eighty-one records remained. After screening for eligibility criteria, there were forty-eight primary research articles with statistically significant data relevant to sirtuins and hearing. Overall, SIRT1 (n = 29) was the most studied sirtuin paralog. Over the last two decades, research on sirtuins and hearing has largely focused on age-, noise-, and drug-induced hearing loss. Past and current studies highlight the role of sirtuins as a mediator of redox homeostasis. However, more studies need to be conducted on the involvement of SIRT2 and SIRT4-7 in hearing protection. Full article

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

Cisplatin is an election chemotherapeutic agent used for many cancer treatments. Its cytotoxicity against neoplastic cells is mirrored by that taking place in healthy cells and tissues, resulting in serious adverse events. A very frequent one is ototoxicity, causing hearing loss which may permanently affect quality of life after successful oncologic treatments. Exacerbated oxidative stress is a main cytotoxic mechanism of cisplatin, including ototoxicity. Previous reports have shown antioxidant protection against cisplatin ototoxicity, but there is a lack of comparative studies on the otoprotectant activity and mechanism of antioxidant formulations. Here, we show evidence that a cocktail of vitamins A, C, and E along with Mg⁺⁺ (ACEMg), previously shown to protect against noise-induced hearing loss, reverses auditory threshold shifts, promotes outer hair cell survival, and attenuates oxidative stress in the cochlea after cisplatin treatment, thus protecting against extreme cisplatin ototoxicity in rats. The addition of 500 mg N-acetylcysteine (NAC), which, administered individually, also shows significant attenuation of cisplatin ototoxicity, to the ACEMg formulation results in functional degradation of ACEMg otoprotection. Mg⁺⁺ administered alone, as MgSO₄, also prevents cisplatin ototoxicity, but in combination with 500 mg NAC, otoprotection is also greatly degraded. Increasing the dose of NAC to 1000 mg also results in dramatic loss of otoprotection activity compared with 500 mg NAC. These findings support that single antioxidants or antioxidant combinations, particularly ACEMg in this experimental series, have significant otoprotection efficacy against cisplatin ototoxicity. However, an excess of combined antioxidants and/or elevated doses, above a yet-to-be-defined “antioxidation threshold”, results in unrecoverable redox imbalance with loss of otoprotectant activity. Full article

Noise-induced hearing loss (NIHL) is a major cause of hearing impairment and is linked to dementia and mental health conditions, yet no FDA-approved drugs exist to prevent it. Downregulating the mitogen-activated protein kinase (MAPK) cellular pathway has emerged as a promising approach to attenuate NIHL, but the molecular targets and the mechanism of protection are not fully understood. Here, we tested specifically the role of the kinases ERK1/2 in noise otoprotection using a newly developed, highly specific ERK1/2 inhibitor, tizaterkib, in preclinical animal models. Tizaterkib is currently being tested in phase 1 clinical trials for cancer treatment and has high oral bioavailability and low predicted systemic toxicity in mice and humans. In this study, we performed dose–response measurements of tizaterkib’s efficacy against permanent NIHL in adult FVB/NJ mice, and its minimum effective dose (0.5 mg/kg/bw), therapeutic index (>50), and window of opportunity (<48 h) were determined. The drug, administered orally twice daily for 3 days, 24 h after 2 h of 100 dB or 106 dB SPL noise exposure, at a dose equivalent to what is prescribed currently for humans in clinical trials, conferred an average protection of 20–25 dB SPL in both female and male mice. The drug shielded mice from the noise-induced synaptic damage which occurs following loud noise exposure. Equally interesting, tizaterkib was shown to decrease the number of CD45- and CD68-positive immune cells in the mouse cochlea following noise exposure. This study suggests that repurposing tizaterkib and the ERK1/2 kinases’ inhibition could be a promising strategy for the treatment of NIHL. Full article

Hearing loss is one of the most common types of disability; however, there is only one FDA-approved drug to prevent any type of hearing loss. Treatment with the highly effective chemotherapy agent, cisplatin, and exposure to high-decibel noises are two of the most common causes of hearing loss. The mitogen-activated protein kinase (MAPK) pathway, a phosphorylation cascade consisting of RAF, MEK1/2, and ERK1/2, has been implicated in both types of hearing loss. Pharmacologically inhibiting BRAF or ERK1/2 is protective against noise- and cisplatin-induced hearing loss in multiple mouse models. Trametinib, a MEK1/2 inhibitor, protects from cisplatin-induced outer hair cell death in mouse cochlear explants; however, to the best of our knowledge, inhibiting MEK1/2 has not yet been shown to be protective against hearing loss in vivo. In this study, we demonstrate that trametinib protects against cisplatin-induced hearing loss in a translationally relevant mouse model and does not interfere with cisplatin’s tumor-killing efficacy in cancer cell lines. Higher doses of trametinib were toxic to mice when combined with cisplatin, but lower doses of the drug were protective against hearing loss without any known toxicity. Trametinib also protected mice from noise-induced hearing loss and synaptic damage. This study shows that MEK1/2 inhibition protects against both insults of hearing loss, as well as that targeting all three kinases in the MAPK pathway protects mice from cisplatin- and noise-induced hearing loss. Full article

Characterising inner ear disorders represents a significant challenge due to a lack of reliable experimental procedures and identified biomarkers. It is also difficult to access the complex microenvironments of the inner ear and investigate specific pathological indicators through conventional techniques. Omics technologies have the potential to play a vital role in revolutionising the diagnosis of ear disorders by providing a comprehensive understanding of biological systems at various molecular levels. These approaches reveal valuable information about biomolecular signatures within the cochlear tissue or fluids such as the perilymphatic and endolymphatic fluid. Proteomics identifies changes in protein abundance, while metabolomics explores metabolic products and pathways, aiding the characterisation and early diagnosis of diseases. Although there are different methods for identifying and quantifying biomolecules, mass spectrometry, as part of proteomics and metabolomics analysis, could be utilised as an effective instrument for understanding different inner ear disorders. This study aims to review the literature on the application of proteomic and metabolomic approaches by specifically focusing on Meniere’s disease, ototoxicity, noise-induced hearing loss, and vestibular schwannoma. Determining potential protein and metabolite biomarkers may be helpful for the diagnosis and treatment of inner ear problems. Full article

Background: It is assumed that speech comprehension deficits in background noise are caused by age-related or acquired hearing loss. Methods: We examined young, middle-aged, and older individuals with and without hearing threshold loss using pure-tone (PT) audiometry, short-pulsed distortion-product otoacoustic emissions (pDPOAEs), auditory brainstem responses (ABRs), auditory steady-state responses (ASSRs), speech comprehension (OLSA), and syllable discrimination in quiet and noise. Results: A noticeable decline of hearing sensitivity in extended high-frequency regions and its influence on low-frequency-induced ABRs was striking. When testing for differences in OLSA thresholds normalized for PT thresholds (PTTs), marked differences in speech comprehension ability exist not only in noise, but also in quiet, and they exist throughout the whole age range investigated. Listeners with poor speech comprehension in quiet exhibited a relatively lower pDPOAE and, thus, cochlear amplifier performance independent of PTT, smaller and delayed ABRs, and lower performance in vowel-phoneme discrimination below phase-locking limits (/o/-/u/). When OLSA was tested in noise, listeners with poor speech comprehension independent of PTT had larger pDPOAEs and, thus, cochlear amplifier performance, larger ASSR amplitudes, and higher uncomfortable loudness levels, all linked with lower performance of vowel-phoneme discrimination above the phase-locking limit (/i/-/y/). Conslusions: This study indicates that listening in noise in humans has a sizable disadvantage in envelope coding when basilar-membrane compression is compromised. Clearly, and in contrast to previous assumptions, both good and poor speech comprehension can exist independently of differences in PTTs and age, a phenomenon that urgently requires improved techniques to diagnose sound processing at stimulus onset in the clinical routine. Full article

Hearing is essential for communication, and its loss can cause a serious disruption to one’s social life. Hearing loss is also recognized as a major risk factor for dementia; therefore, addressing hearing loss is a pressing global issue. Sensorineural hearing loss, the predominant type of hearing loss, is mainly due to damage to the inner ear along with a variety of pathologies including ischemia, noise, trauma, aging, and ototoxic drugs. In addition to genetic factors, oxidative stress has been identified as a common mechanism underlying several cochlear pathologies. The cochlea, which plays a major role in auditory function, requires high-energy metabolism and is, therefore, highly susceptible to oxidative stress, particularly in the mitochondria. Based on these pathological findings, the potential of antioxidants for the treatment of hearing loss has been demonstrated in several animal studies. However, results from human studies are insufficient, and future clinical trials are required. This review discusses the relationship between sensorineural hearing loss and reactive oxidative species (ROS), with particular emphasis on age-related hearing loss, noise-induced hearing loss, and ischemia–reperfusion injury. Based on these mechanisms, the current status and future perspectives of ROS-targeted therapy for sensorineural hearing loss are described. Full article

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

The aim of the present study was to investigate adverse effects of head injury, neck trauma, and chronic noise exposure on the complaint profile in people with Ménière’s disease (MD). The study used a retrospective design. Register data of 912 patients with MD from the Finnish Ménière Federation database were studied. The data comprised case histories of traumatic brain injury (TBI), neck trauma and occupational noise exposure, MD specific complaints, impact related questions, and the E-Qol health-related quality of life instrument. TBI was classified based on mild, moderate, and severe categories of transient loss of consciousness (TLoC). The mean age of the participants was 60.2 years, the mean duration of the disease was 12.6 years, and 78.7% were females. Logistic regression analysis, linear correlation, and pairwise comparisons were used in evaluating the associations. 19.2% of the participants with MD had a history of TBI. The phenotype of participants with TBI was associated with frequent vestibular drop attacks (VDA), presyncope, headache-associated vertigo, and a reduction in the E-QoL. Logistic regression analysis explained the variability of mild TBI in 6.8%. A history of neck trauma was present in 10.8% of the participants. Neck trauma associated with vertigo (NTwV) was seen in 47 and not associated with vertigo in 52 participants. The phenotype of NTwV was associated with balance problems, VDA, physical strain-induced vertigo, and hyperacusia. Logistic regression analysis explained 8.7% of the variability of the complaint profile. Occupational noise exposure was recorded in 25.4% of the participants and correlated with the greater impact of tinnitus, hyperacusis, and hearing loss. Neither the frequency, duration, or severity of vertigo or nausea were significantly different between the baseline group and the TBI, NTwV, or noise-exposure groups. The results indicate that TBI and NTwV are common among MD patients and may cause a confounder effect. Full article