Puerarin inhibits cisplatin-induced ototoxicity in mice through regulation of TRPV1-dependent calcium overload.

Puerarin (PUE), a flavonoid derivative with vasodilatory effects found in the traditional Chinese medicine kudzu, has anti-sensorineural hearing loss properties. However, the mechanism of its protective effect against ototoxicity is not well understood. In this study, we used in vitro and in vivo methods to investigate the protective mechanism of puerarin against cisplatin (CDDP)-induced ototoxicity. We established an ototoxicity model of CDDP in BALB/c mice and assessed the degree of hearing loss and cochlear cell damage. We used bioinformatics analysis, molecular docking, histological analysis, and biochemical and molecular biology to detect the expression of relevant factors. Our results show that puerarin improved CDDP-induced hearing loss and reduced hair cell loss. It also blocked CDDP-induced activation of TRPV1 and inhibited activation of IP3R1 to prevent intracellular calcium overload. Additionally, puerarin blocked CDDP-stimulated p65 activation, reduced excessive ROS production, and alleviated cochlear cell apoptosis. Our study provides new evidence and potential targets for the protective effect of puerarin against drug-induced hearing loss. Puerarin ameliorates cisplatin-induced ototoxicity and blocks cellular apoptosis by inhibiting CDDP activated TRPV1/IP3R1/p65 pathway, blocking induction of calcium overload and excessive ROS expression.

Suplementação de zinco para cocleovestibulopatias: sinopse baseada em evidências / Zinc supplementation for cochleovestibulopathies: evidence-based synopsis

Contexto: O zinco é um elemento-traço que age no sistema auditivo, atuando em sinapses auditivas e na cóclea, sobretudo junto à enzima superóxido dismutase. Objetivo: Avaliar a efetividade da suplementação de zinco para o tratamento de cocleovestibulopatias. Material e Métodos: Trata-se de sinopse baseada em evidências. Procedeu-se à busca por estudos que associavam zinco à perda auditiva, tontura e zumbido em três bases eletrônicas de dados: Cochrane - Central de Registros de Ensaios Clínicos - CENTRAL (2022), PubMed (1966- 2022) e Portal BVS (1982-2022). Dois pesquisadores independentemente extraíram os dados e avaliaram a qualidade dos estudos para a síntese. Os desfechos de análise envolveram melhora de perda auditiva, tontura e zumbido. Resultados: Foram encontrados 231 estudos. Cinco estudos (quatro ensaios clínicos randomizados e uma revisão sistemática) envolvendo um total de 249 pacientes. Discussão: A literatura mundial apresenta poucos estudos relacionando zinco e cocleovestibulopatias. A maioria trata-se de estudos in vitro ou de experimentação animal. Os estudos em humanos são ensaios clínicos de baixa amostragem e elevada heterogeneidade, que avaliaram melhora de perda auditiva e melhora de zumbido. Nenhum estudo avaliou melhora da tontura. O nível de evidência é muito baixo e não permite, nesse momento, aferir a efetividade do zinco para tratamento de cocleovestibulopatias em humanos, sendo sua utilização clínica baseada na experiência de cada profissional. Conclusões: Não há evidência de efetividade da suplementação de zinco no tratamento de cocleovestibulopatias, sendo recomendada a realização de novos estudos de boa qualidade metodológica. PALAVRAS-CHAVE: Zinco, perda auditiva, tontura, zumbido, prática clínica baseada em evidências

A Prospective Study of the Effect of Tinnitus Sound Matching Degree on the Efficacy of Customized Sound Therapy in Patients with Chronic Tinnitus.

OBJECTIVES: The aim of this study was to explore and compare the customized sound therapy effect between tinnitus sound matching and nonmatching patients in tinnitus customized sound therapy and therapy-related influencing factors. METHODS: This prospective study investigated a total of 100 patients with unilateral chronic tinnitus who received customized sound therapy. The participants were dichotomously divided into matching (group A) and nonmatching (group B) groups after 4 stages of tinnitus matching via the tinnitus assistant app (provided by Sound Ocean Company, SuZhou, China). Each group consists of 50 participants. Before and 6 months after the treatment, Hospital Anxiety and Depression Scale (HADS), tinnitus handicap inventory (THI), and tinnitus loudness Visual Analog Scale (VAS) were used to evaluate the customized sound therapy effect and explore other related influencing factors. RESULTS: (1) The HADS-A, HADS-D, THI, and VAS scores of 2 groups were both significantly decreased after treatment. (2) The HADS-A and THI scores improved markedly in group A than that in group B, which could be related to the hearing loss of the tinnitus side ear before treatment; the lighter the degree of hearing loss, the better the improvement. No statistically significant differences were detected in HADS-D and VAS scores between the 2 groups, and also, these were not related to the degree of hearing loss. The differences in age, gender, and tinnitus duration did not show any statistically significant effect on the improvement of the 2 groups. CONCLUSIONS: Both tinnitus sound matching and nonmatching of the customized sound therapy brought a significant effect to tinnitus participants. Our study also suggests that THI and HADS-A scores of those with tinnitus matching participants improved markedly as compared to those of nonmatching participants, and the customized sound therapy effect is negatively correlated with the severity of hearing loss.

Maternal knowledge and views regarding early hearing detection and intervention in children aged 0-5 years at a semi-urban primary care clinic in South Africa.

BACKGROUND: South Africans have an increasing burden of hearing loss, especially in low-income rural areas. Limited information is available regarding caregivers' knowledge and views regarding infant hearing loss, which is essential for the successful implementation of early hearing detection and intervention (EHDI) programmes. OBJECTIVES: The main aim of the study was to describe the knowledge and views of mothers with children aged between 0 and 5 years old regarding hearing screening, risk factors, symptoms of hearing loss, and intervention options for hearing loss. METHOD: A survey was employed at a primary care clinic to gain insight into the maternal views on hearing loss and early intervention services for children aged 0-5 years old. RESULTS: The majority (83.2%) of the mothers believed that hearing can be tested at birth, 90.7% believed in the biomedical model of intervention which is based on cure, prevention, and pathology as opposed to traditional or alternative medicinal beliefs, and 95.3% indicated that they would seek medical attention if they noticed symptoms of hearing loss. Consequences of hearing loss, such as academic, communication and social problems, were indicated by 65.4% of mothers. CONCLUSION: The findings demonstrated that although cultural beliefs regarding superstitious causes of hearing loss and use of traditional medicine exist, satisfactory maternal knowledge regarding detection and intervention for hearing loss is present. Maternal views are favourable and a general willingness to participate in EHDI programmes was present. This study advocates for the implementation of EHDI programmes at all primary healthcare clinics across South Africa.

Associations of Dietary Riboflavin, Niacin, and Retinol with Age-related Hearing Loss: An Analysis of Korean National Health and Nutrition Examination Survey Data.

Because age-related hearing loss (ARHL) is irreversible, prevention is very important. Thus, investigating modifying factors that help prevent ARHL is critical for the elderly. Nutritional status or nutritional factors for the elderly are known to be associated with many problems related to aging. Emerging studies suggest that there was the interaction between nutrition and ARHL. We aimed to investigate the possible impact of dietary nutrients on ARHL using data from the fifth Korean National Health and Nutrition Examination Survey (KNHANES) which included 4742 subjects aged ≥ 65 years from 2010 to 2012. All participants underwent an otologic examination, audiologic evaluation, and nutritional survey. The associations between ARHL and nutrient intake were analyzed using simple and multiple regression models with complex sampling adjusted for confounding factors, such as BMI, smoking status, alcohol consumption, and history of hypertension and diabetes. Higher intake groups of riboflavin, niacin and retinol was inversely associated with ARHL prevalence (riboflavin aOR, 0.71; 95% CI, 0.54-0.94; p = 0.016, niacin aOR, 0.72; 95% CI, 0.54-0.96; p = 0.025, retinol aOR 0.66; 95% CI, 0.51-0.86; p = 0.002, respectively). Our findings suggest the recommended intake levels of riboflavin, niacin, and retinol may help reduce ARHL in the elderly.

[Reactions in the organ of Corti to electrical stimulation : StED technology for detecting changes]. / Reaktionen im Corti-Organ auf elektrische Stimulation : StED-Technologie zum Nachweis von Veränderungen.

Increasing numbers of cochlear implant patients have residual hearing. Despite surgical and pharmacological efforts to preserve residual hearing, a significant number of these patients suffer a late, unexplained loss of residual hearing. Surgical trauma can be excluded as the cause. To investigate this phenomenon and because cells in their native environment react differently to stimuli (such as electrical current) than isolated cells, whole-organ explants from cochleae may be a better model. For early detection of synaptic changes in the organ of Corti, a high-resolution microscopic technique such as stimulated emission depletion (StED) can be used. The aim of this study was establishment of a qualitative and quantitative technique to determinate changes in the organ of Corti and its synapses after electrical stimulation. Explanted organs of Corti from postnatal rats (P2-4) were cultured on a coverslip for 24 h and subsequently exposed to biphasic pulsed electrical stimulation (amplitude 0.44-2.0 mA, pulse width 400 µs, interpulse delay 120 µs, repetition 1 kHz) for another 24 h. For visualization, the cytoskeleton and the ribbon synapses were stained immunocytochemically. For an early detectable response to electrical stimulation, the number of synapses was quantified. Organs of Corti without electrical stimulation served as a reference. Initial research has shown that electrical stimulation can cause changes in ribbon synapses and that StED can detect these alterations. The herein established model could be of great importance for identification of molecular changes in the organ of Corti in response to electrical or other stimuli.

Association of Coffee Consumption with Hearing and Tinnitus Based on a National Population-Based Survey.

Coffee is the one of the most common beverages worldwide and has received considerable attention for its beneficial health effects. However, the association of coffee with hearing and tinnitus has not been well studied. The aim of this study was to investigate the association of coffee with hearing and tinnitus based on a national population-based survey. We evaluated hearing and tinnitus data from the 2009⁻2012 Korean National Health and Nutrition Examination Survey and their relationship with a coffee consumption survey. All patients underwent a medical interview, physical examination, hearing test, tinnitus questionnaire and nutrition examination. Multivariable logistic regression models were used to examine the associations between coffee and hearing loss or tinnitus. We evaluated 13,448 participants (≥19 years) participants. The frequency of coffee consumption had a statistically significant inverse correlation with bilateral hearing loss in the 40⁻64 years age group. Daily coffee consumers had 50⁻70% less hearing loss than rare coffee consumers, which tended to be a dose-dependent relationship. In addition, the frequency of coffee consumption had an inverse correlation with tinnitus in the 19⁻64 years age group but its association was related with hearing. Brewed coffee had more of an association than instant or canned coffee in the 40⁻64 years age group. These results suggest a protective effect of coffee on hearing loss and tinnitus.

Development of Second-Generation CDK2 Inhibitors for the Prevention of Cisplatin-Induced Hearing Loss.

There are currently no FDA-approved therapies to prevent the hearing loss associated with the usage of cisplatin in chemotherapeutic regimens. We recently demonstrated that the pharmacologic inhibition with kenpaullone or genetic deletion of CDK2 preserved hearing function in animal models treated with cisplatin, which suggests that CDK2 is a promising therapeutic target to prevent cisplatin-induced ototoxicity. In this study, we identified two lead compounds, AT7519 and AZD5438, from a focused library screen of 187 CDK2 inhibitors, performed in an immortalized cell line derived from neonatal mouse cochleae treated with cisplatin. Moreover, we screened 36 analogues of AT7519 and identified analogue 7, which exhibited an improved therapeutic index. When delivered locally, analogue 7 and AZD5438 both provided significant protection against cisplatin-induced ototoxicity in mice. Thus, we have identified two additional compounds that prevent cisplatin-induced ototoxicity in vivo and provided further evidence that CDK2 is a druggable target for treating cisplatin-induced ototoxicity.

l-N-acetylcysteine protects outer hair cells against TNFα initiated ototoxicity in vitro.

OBJECTIVE: The present study is aimed at determining the efficacy and exploring the mechanisms by which l-N-acetylcysteine (l-NAC) provides protection against tumor necrosis factor-alpha (TNFα)-induced oxidative stress damage and hair cell loss in 3-day-old rat organ of Corti (OC) explants. Previous work has demonstrated a high level of oxidative stress in TNFα-challenged OC explants. TNFα can potentially play a significant role in hair cell loss following an insult to the inner ear. l-NAC has shown to provide effective protection against noise-induced hearing loss in laboratory animals but mechanisms of this otoprotective effect are not well-defined. DESIGN: Rat OC explants were exposed to either: (1) saline control (N = 12); (2) TNFα (2 µg/ml, N = 12); (3) TNFα+l-NAC (5 mM, N = 12); (4) TNFα+l-NAC (10 mM, N = 12); or (5) l-NAC (10 mM, N = 12). Outer hair cell (OHC) density, levels of reactive oxygen species (ROS), lipid peroxidation of cell membranes, gluthathione activity, and mitochondrial viability were assayed. RESULTS: l-NAC (5 and 10 mM) provided protection for OHCs from ototoxic level of TNFα in OC explants. Groups treated with TNFα+l-NAC (5 mM) showed a highly significant reduction of both ROS (p < 0.01) and 4-hydroxy-2-nonenal immunostaining (p < 0.001) compared to TNFα-challenged explants. Total glutathione levels were low in TNFα-challenged explants compared to control and TNFα+l-NAC (5 mM) treated explants (p < 0.001). CONCLUSIONS: l-NAC is a promising treatment for protecting auditory HCs from TNFα-induced oxidative stress and subsequent loss via programmed cell death.

Early childhood undernutrition increases risk of hearing loss in young adulthood in rural Nepal.

Background: Prevalence of young adult hearing loss is high in low-resource societies; the reasons for this are likely complex but could involve early childhood undernutrition. Objective: We evaluated preschool childhood stunting, wasting, and underweight as risk factors for hearing loss in young adulthood in Sarlahi District, southern Nepal. Design: Ear health was assessed in 2006-2008 in a cohort of 2193 subjects aged 16-23 y, who as children <60 mo of age participated in a 16-mo placebo-controlled, randomized vitamin A supplementation trial from 1989 to 1991. At each of five 4-mo assessments, field staff measured children's weight, height, and mid-upper arm circumference (MUAC) and recorded validated parental history of ear discharge in the previous 7 d. Children were classified as stunted [<-2 z score height-for-age (HAZ)], underweight [<-2 z score weight-for-age (WAZ)], or wasted [<-2 z score MUAC-for-age (MUACAZ) or body mass index-for-age (BMIAZ)]. At follow-up, hearing was tested by audiometry and tympanometry, with hearing loss defined as pure-tone average >30dB in the worse ear (0.5, 1, 2, 4 kHz) and middle-ear dysfunction as abnormal tympanometric peak height (<0.3 or >1.4 mmho) or width (<50 or >110 daPa). Results: Hearing loss, present in 5.9% (95% CI: 5.01%, 7.00%) of subjects, was associated with early childhood stunting (OR: 1.64; 95% CI: 1.10, 1.45), underweight (OR: 1.70; 95% CI: 1.18, 2.44) and wasting by BMIAZ (OR: 1.88; 95% CI: 1.19, 2.97) and MUACAZ (OR: 2.14; 95% CI: 1.47, 3.12). Abnormal tympanometry, affecting 16.6% (95% CI: 15.06%, 18.18%), was associated with underweight (OR: 1.46; 95% CI: 1.16, 1.84) and wasting by BMIAZ (OR: 1.80; 95% CI: 1.32, 2.46) and MUACAZ (OR: 1.42; 95% CI: 1.10, 1.84), but not stunting (OR: 1.18; 95% CI: 0.93, 1.49) in early childhood. Highest ORs were observed for subjects with both hearing loss and abnormal tympanometry, ranging from 1.87 to 2.24 (all lower 95% CI >1.00). Conclusions: Early childhood undernutrition is a modifiable risk factor for early adulthood hearing loss.

The Development of a Nano-based Approach to Alleviate Cisplatin-Induced Ototoxicity.

Cisplatin-induced hearing loss is experienced by a high percentage of patients with squamous cell carcinoma undergoing cisplatin chemotherapy. A novel nano-construct capable of sequestering extracellular cisplatin was developed to combat this problem. The nano-construct consisted of superparamagnetic iron oxide nanoparticles (SPIONs) entrapped within polymeric micelles, which were formed from a glutathione diethyl ester-conjugated amphiphilic diblock copolymer. The glutathione-micelles were analyzed at the cellular level and in an organotypic study for safety evaluation. All utilized methods indicated that the micelles do not cause cellular toxicity or organ damage. The micelles' ability to reduce cisplatin-induced cytotoxicity was then probed in an in vitro model. Cisplatin was pre-treated with the novel nano-construct before being added to growing cells. When compared to cells that were exposed to untreated cisplatin, cells in the pre-treated cisplatin group showed a significant increase in cell viability. This clearly demonstrates that the construct is able to protect the cells from cisplatin cytotoxicity and makes it highly likely that the novel nano-construct will be able to play a role in the protection of the inner ear from cisplatin-induced ototoxicity.

Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents.

Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9-guide RNA-lipid complexes targeting the Tmc1Bth allele into the cochlea of neonatal Tmc1Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+ mice. These findings suggest that protein-RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.

Evaluation of Mitoquinone for Protecting Against Amikacin-Induced Ototoxicity in Guinea Pigs.

HYPOTHESIS: Mitoquinone (MitoQ) attenuates amikacin ototoxicity in guinea pigs. BACKGROUND: MitoQ, a mitochondria-targeted derivative of the antioxidant ubiquinone, has improved bioavailability and demonstrated safety in humans. Thus, MitoQ is a promising therapeutic approach for protecting against amikacin-induced ototoxicity. METHODS: Both oral and subcutaneous administrations of MitoQ were tested. Amikacin-treated guinea pigs (n = 12-18 per group) received water alone (control) or MitoQ 30 mg/l-supplemented drinking water; or injected subcutaneously with 3 to 5 mg/kg MitoQ or saline (control). Auditory brainstem responses and distortion product otoacoustic emissions were measured before MitoQ or control solution administration and after amikacin injections. Cochlear hair cell damage was assessed using scanning electron microscopy and Western blotting. RESULTS: With oral administration, animals that received 30 mg/l MitoQ had better hearing than controls at only 24 kHz at 3-week (p = 0.017) and 6-week (p = 0.027) post-amikacin. With subcutaneous administration, MitoQ-injected guinea pigs had better hearing than controls at only 24 kHz, 2-week post-amikacin (p = 0.013). Distortion product otoacoustic emission (DPOAE) amplitudes were decreased after amikacin injections, but were not different between treatments (p > 0.05). Electron microscopy showed minor difference in outer hair cell loss between treatments. Western blotting demonstrated limited attenuation of oxidative stress in the cochlea of MitoQ-supplemented guinea pigs. CONCLUSIONS: Oral or subcutaneous MitoQ provided limited protection against amikacin-induced hearing loss and cochlear damage in guinea pigs. Other strategies for attenuating aminoglycoside-induced ototoxicity should be explored.

Phenotypic Optimization of Urea-Thiophene Carboxamides To Yield Potent, Well Tolerated, and Orally Active Protective Agents against Aminoglycoside-Induced Hearing Loss.

Hearing loss is a major public health concern with no pharmaceutical intervention for hearing protection or restoration. Using zebrafish neuromast hair cells, a robust model for mammalian auditory and vestibular hair cells, we identified a urea-thiophene carboxamide, 1 (ORC-001), as protective against aminoglycoside antibiotic (AGA)-induced hair cell death. The 50% protection (HC50) concentration conferred by 1 is 3.2 µM with protection against 200 µM neomycin approaching 100%. Compound 1 was sufficiently safe and drug-like to validate otoprotection in an in vivo rat hearing loss model. We explored the structure-activity relationship (SAR) of this compound series to improve otoprotective potency, improve pharmacokinetic properties and eliminate off-target activity. We present the optimization of 1 to yield 90 (ORC-13661). Compound 90 protects mechanosensory hair cells with HC50 of 120 nM and demonstrates 100% protection in the zebrafish assay and superior physiochemical, pharmacokinetic, and toxicologic properties, as well as complete in vivo protection in rats.

Pomegranate peel extract attenuates D-galactose-induced oxidative stress and hearing loss by regulating PNUTS/PP1 activity in the mouse cochlea.

Oxidative stress is considered to be a major contributor to age-related hearing loss (ARHL). Here, we investigated whether pomegranate peel extract (PPE) protected against hearing loss by decreased oxidative stress in the cochlea of D-galactose-induced accelerated aging mice. The aging mice exhibited an increase in hearing threshold shifts and hair cells loss, which were improved in the PPE-treated aging mice. The aging mice also exhibited an increase in 4-hydroxynonenal, the expression of protein phosphatase 1 nuclear targeting subunit (PNUTS), p53 and caspase-3, and a decrease in protein phosphatase 1 (PP1) and MDM2 in the cochlea. PPE treatment reversed the changes in aforementioned molecules. Our results suggested that PPE can protect against ARHL, the underlying mechanisms may involve in the inhibition of oxidative damage of cochlea, possibly by regulating PNUTS/PP1 pathway. The results from the present study provide a new therapeutic strategy to use PPE for prevention of ARHL.

Retroauricular Approach for Targeted Cochlear Therapy Experiments in Wistar Albino Rats.

BACKGROUND: As the idea of stem cell technology in the treatment of sensorial hearing loss has emerged over the past decades, the need for in vivo models for related experiments has become explicit. One of the most common experimental models for inner ear stem cell delivery experiments is the Wistar albino rat. AIMS: To investigate the surgical anatomy of the temporal bone of the Wistar albino rat with respect to the dissection steps, operative techniques and potential pitfalls of surgery. STUDY DESIGN: Animal experimentation. METHODS: Adult Wistar albino rats were operated on via the retroauricular approach under an operation microscope. The anatomy of the temporal bone, the surgical route to the temporal bulla and the inner ear were investigated. Technical details of surgical steps, complications and potential pitfalls during the surgery were noted. RESULTS: The study group consisted of 40 adult Wistar albino rats. The mean times to reach the bulla and to achieve cochleostomy were 4.3 (2-13 min) and 7.5 min (3.5-22 min), respectively. The mean width of the facial nerve was 0.84 mm (0.42-1.25 mm). The stapedial artery lay nearly perpendicular to the course of the facial nerve (88-93 °C). There were three major complications: two large cochleostomies and one massive bleed from the stapedial artery. CONCLUSION: The facial nerve was the key anatomical landmark in locating the bulla. By retrograde tracing of the facial nerve, it was possible to find the bulla ventral (inferior) to the main trunk. The facial nerve trunk was the upper limit when drilling the bulla. By dissecting the main trunk of the facial nerve and retracting cranially, a large drilling space could be achieved. Our results suggest that the retroauricular approach is an effective, feasible route for inner ear drug delivery experiments in Wistar albino rats.

Fractionated vs. single-fraction stereotactic radiotherapy in patients with vestibular schwannoma : Hearing preservation and patients' self-reported outcome based on an established questionnaire.

BACKGROUND: Stereotactic radiotherapy (RT) has been established as a valid treatment alternative in patients with vestibular schwannoma (VS). There is ongoing controversy regarding the optimal fractionation. Hearing preservation may be the primary goal for patients with VS, followed by maintenance of quality of life (QoL). METHODS: From 2002 to 2015, 184 patients with VS were treated with radiosurgery (RS) or fractionated stereotactic radiotherapy (FSRT). A survey on current symptoms and QoL was conducted between February and June 2016. RESULTS: Median follow-up after RT was 7.5 years (range 0-14.4 years). Mean overall survival (OS) after RT was 31.1 years, with 94 and 87% survival at 5 and 10 years, respectively [corrected]. Mean progression-free survival (PFS) was 13.3 years, with 5­ and 10-year PFS of 92%. Hearing could be preserved in RS patients for a median of 36.3 months (range 2.3-13.7 years). Hearing worsened in 17 (30%) cases. Median hearing preservation for FSRT was 48.7 months (range 0.0-13.8 years); 29 (23%) showed hearing deterioration. The difference in hearing preservation was not significant between RS and FSRT (p = 0.3). A total of 123/162 patients participated in the patient survey (return rate 76%). The results correlate well with the information documented in the patient files for tinnitus and facial and trigeminal nerve toxicity. Significant differences appeared regarding hearing impairment, gait uncertainty, and imbalance. CONCLUSION: These data confirm that RS and FSRT are comparable in terms of local control for VS. RS should be reserved for smaller lesions, while FSRT can be offered independently of tumor size. Patient self-reported outcome during follow-up is of high value. The established questionnaire could be validated in the independent cohort.

Coenzyme Q10 plus Multivitamin Treatment Prevents Cisplatin Ototoxicity in Rats.

Cisplatin (Cpt) is known to induce a high level of oxidative stress, resulting in an increase of reactive oxygen species damaging the inner ear and causing hearing loss at high frequencies. Studies on animal models show that antioxidants may lower Cpt-induced ototoxicity. The aim of this study is to evaluate the ototoxic effects of two different protocols of Cpt administration in a Sprague-Dawley rat model, and to test in the same model the synergic protective effects of a solution of coenzyme Q10 terclatrate and Acuval 400®, a multivitamin supplement containing antioxidant agents and minerals (Acu-Qter). The Cpt was administered intraperitoneally in a single dose (14 mg/kg) or in three daily doses (4.6 mg/kg/day) to rats orally treated or untreated with Acu-Qter for 5 days. The auditory function was assessed by measuring auditory brainstem responses from 2 to 32 kHz at day 0 and 5 days after treatment. Similar hearing threshold and body weight alterations were observed in both Cpt administration protocols, but mortality reduced to zero when Cpt was administered in three daily doses. The Acu-Qter treatment was able to prevent and completely neutralize ototoxicity in rats treated with three daily Cpt doses, supporting the synergic protective effects of coenzyme Q terclatrate and Acuval 400® against Cpt-induced oxidative stress. The administration protocol involving three Cpt doses is more similar to common human chemotherapy protocols, therefore it appears more useful for long-term preclinical studies on ototoxicity prevention.

Protective Effect of Korean Red Ginseng on Cisplatin Ototoxicity: Is It Effective Enough?

OBJECTIVE: The aim of our study was to investigate the effects Korean Red Ginseng (KRG) on cisplatin (CDDP) ototoxicity in vivo and in vitro. MATERIALS AND METHODS: The first part of the study was conducted on the House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line. Cells were treated with CDDP, KRG, and their combination for 24 h. Cell viability, apoptosis, and the expression of 84 apoptosis-related genes were analyzed. In the second part of the study, 30 Wistar albino rats were divided into five groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were obtained. In groups I, II, and III, only saline, KRG, and CDDP, respectively, were given. In group IV, 500 mg/kg KRG and in group V, 150 mg/kg of KRG were administered for 10 days. In groups III, IV, and V, 16 mg/kg CDDP injections were administered on day 11. On day 14, final DPOAEs and ABR measurements were completed. The rats were then sacrificed, and their inner ear structures were evaluated by transmission electron microscopy. RESULTS: In the first part of the study, pretreatment with 1 mg/mL KRG protected cells from CDDP ototoxicity. This protection was mainly due to a decline in apoptotic gene expression and an increase in antiapoptotic gene expression. In the in vivo part of the study, we found that both KRG doses had otoprotective effects. This protection was more prominent at the lower dose, especially on the spiral ganglion and the brainstem. CONCLUSION: KRG was shown to be an otoprotective agent against CDDP-induced ototoxicity both in vivo and in vitro.

Vitamin E neuroprotection against cisplatin ototoxicity: Preliminary results from a randomized, placebo-controlled trial.

BACKGROUND: Few studies have investigated the effect of vitamin E in reducing the cisplatin (CDDP)-induced ototoxicity. This study evaluated vitamin E supplementation as a protecting agent against CDDP-induced ototoxicity. METHODS: Patients who started CDDP were randomly assigned to receive vitamin E supplementation at 400 mg per day (group 1) or placebo (group 2). Audiograms and evoked brainstem responses were obtained at baseline, and after 1, 2, and 3 months. RESULTS: Twenty-three patients affected by solid malignancies were enrolled (13 in group 1 and 10 in group 2). At 1 month, a significant hearing loss in group 2 at both 2000 HZ (right ear: p = .05; left ear: p = .04) and 8000 HZ (right ear: p = .04; left ear: p = .03) was detected when compared to baseline values. Audiograms did not show significant changes. At 1 month, evoked brainstem responses remained unchanged in both arms without significant differences between groups. CONCLUSION: These preliminary findings confirm the neuroprotective properties of vitamin E against the CDDP-induced ototoxicity. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2118-E2121, 2016.