Ototoxicity among cisplatin, carboplatin, and oxaliplatin in zebrafish model.

Platinum-based antineoplastic drugs, including cisplatin, carboplatin, and oxaliplatin, are widely used in the treatment of various cancers. Ototoxicity is a common adverse effect of platinum-based drugs. Ototoxicity leads to irreversible hearing impairment. We hypothesize that different platinum-based drugs exhibit varying ototoxic concentrations, time effects, and ototoxic mechanisms. We tested this hypothesis by using a zebrafish model (pvalb3b: TagGFP) to assess the viability of hair cells collected from zebrafish larvae. Cisplatin, carboplatin, and oxaliplatin were administered at dosages of 100, 200, or 400 µM, and the ototoxic effects of these drugs were assessed 1, 2, or 3 h after administration. Fm4-64 and a TUNEL assay were used to label the membranes of living hair cells and to detect cell apoptosis, respectively. We observed that >50% of hair cells were damaged at 1 h after cisplatin (100 µM) exposure, and this ototoxic effect increased at higher dosages and over time. Owing to the smaller ototoxic effects of carboplatin and oxaliplatin, we conducted higher-strength and longer-duration experiments with these drugs. Neither carboplatin nor oxaliplatin was obviously ototoxic, even at 1600 µM and after 6 h. Moreover, only cisplatin damaged the membranes of the hair cells. Cell apoptosis and significantly increased antioxidant gene expression were observed in only the cisplatin group. In conclusion, cisplatin significantly damages sensory hair cells and has notable dosage and time effects. Carboplatin and oxaliplatin are less ototoxic than cisplatin, likely due to having different ototoxic mechanisms than cisplatin.

Risk factors associated with occupational noise-induced hearing loss in the Hispanic community health study/study of Latinos: A cross-sectional epidemiologic investigation.

The purpose of this study was to estimate the prevalence of occupational noise exposure and risk factors of occupational noise-induced hearing loss (NIHL) in Hispanic/Latino adults included in the baseline wave of the Hispanic Community Health Study/Study of Latinos collected from 2008 to 2011. Sequential multiple linear regression modeled the relationship between occupational NIHL (defined as a 3-, 4-, 6-kHz pure-tone average [PTA]) and occupation type, self-reported noise exposure, cardiovascular disease (CVD) risk score, and hearing protective device (HPD) use. The final model controlled for sex, age, and recreational noise exposure. Among 12,851 included participants, approximately 40% (n = 5036) reported occupational noise exposure "Sometimes" (up to 50% of the time) or "Frequently" (75-100% of the time). In the final fitted model, longest-held occupation and CVD risk were associated with poorer hearing. Specifically, those in non-skilled, service, skilled, and military/police/other job categories had between 2.07- and 3.29-dB worse PTA than professional/office workers. Additionally, a shift in the CVD risk score category from low to medium was associated with a 2.25- and 8.20-dB worse PTA for medium and high CVD risk, respectively. Age and sex were also significantly associated with poorer hearing, such that men presented with 6.08 dB worse PTA than women, and for every one-year increase in age, PTA increased by 0.62 dB (ps < .001). No interactions were seen between noise*sometimes or frequent exposure to other ototoxic agents and PTA (ps = .33 & .92, respectively). The prevalence of occupational noise exposure was high in this cross-sectional investigation of adults from Hispanic/Latino backgrounds. Findings contribute to the extant literature by demonstrating that risk factors for occupational NIHL in adults from varying Hispanic/Latino backgrounds are consistent with those of other previously studied groups.

Progress in protecting vestibular hair cells.

Vestibular hair cells are mechanosensory receptors that are capable of detecting changes in head position and thereby allow animals to maintain their posture and coordinate their movement. Vestibular hair cells are susceptible to ototoxic drugs, aging, and genetic factors that can lead to permanent vestibular dysfunction. Vestibular dysfunction mainly results from the injury of hair cells, which are located in the vestibular sensory epithelium. This review summarizes the mechanisms of different factors causing vestibular hair cell damage and therapeutic strategies to protect vestibular hair cells.

Baseline audiological profiling of South African females with cervical cancer: an important attribute for assessing cisplatin-associated ototoxicity.

BACKGROUND: Cisplatin is a popular antineoplastic agent used to treat cervical cancer in women from low and middle-income countries. Cisplatin treatment is associated with ototoxicity, often resulting in hearing loss. In light of this, it is crucial to conduct baseline audiological assessments prior to treatment initiation in order to evaluate the extent of cisplatin-associated-ototoxicity. Additionally, the identification of inherent risk factors and hearing patterns in specific patient cohorts is needed, especially in South Africa, a middle-income country characterized by the quadruple burden of disease (Human Immunodeficiency Virus (HIV), Tuberculosis (TB), Diabetes and Hypertension). METHODS: This study aimed to describe a profile of risk factors and hearing in a cohort of females with cervical cancer before cisplatin treatment commenced. A descriptive study design that included 82 cervical cancer patients, who underwent audiological evaluation prescribed for ototoxicity monitoring was conducted. RESULTS: All participants (n = 82) presented with risk factors (diabetes, hypertension, HIV, and antiretroviral therapy) for cisplatin ototoxicity and/or pre-existing sensorineural hearing loss. High-frequency tinnitus was the most common otological symptom experienced by 25 (31%) participants. Fifty-nine (72%) participants presented with normal hearing, twenty-two (27%) with a sensorineural hearing loss, and 36% were diagnosed with mild hearing loss. Abnormal Distortion Product Otoacoustic Emissions (DPOAE) findings were obtained bilaterally in two participants (2.4%), in the right ear only of another two (2.4%) participants and the left ear of three participants (3.7%). Most participants (94%) had excellent word recognition scores, demonstrating an excellent ability to recognize words within normal conversational levels under optimal listening conditions. Age was significantly associated with hearing loss at all thresholds. Among the co-morbidities, an HIV positive status significantly triggered hearing loss, especially at higher frequencies. CONCLUSION: This study demonstrated that South African females with cervical cancer present with various co-morbidities, which may predispose them to develop cisplatin-associated -ototoxic hearing loss. Identification of these co-morbidities and hearing loss is essential for the accurate monitoring of cisplatin toxicities. Appropriate management of these patients is pivotal to reduce the adverse effects that hearing impairment can have on an individual's quality of life and to facilitate informed decision-making regarding the commencement of cisplatin chemotherapy.

[Objective parameters of auditory function in premature infants in the first year of life after taking ototoxic antibiotics]. / Ob"ektivnye pokazateli slukhovoi funktsii u nedonoshennykh detei pervogo goda zhizni posle priema ototoksicheskikh antibiotikov.

OBJECTIVE: To compare the condition of auditory function during the first year of life according to the registration of distortion product otoacoustic emission (DPOAE) and short-latency evoked potentials (SLEP) in premature infants who received ototoxic antibiotics to those ones, who did not. MATERIAL AND METHODS: Auditory function was examined in 145 premature infants. Auditory assessment was carried out by registration of DPOAEs, SLEPs and tympanometry. Statistical processing was performed using the program Statgraphics Centurion XV. RESULTS: In this study, according to DPOAE, the average response values of the cochlea in premature infants who had a history of ototoxic therapy, undergo final changes after children reach the age of 6 months. The study of latent periods and threshold values of the V peak of SLEP showed a delay in the maturation process of the perceiving and conducting auditory structures during the first year of life in children who received ototoxic antibiotics in the first month of life. CONCLUSION: We evaluated the timing of the completion of response changes in children of the control group using the DPOAE and SLEP registration data. In children of the study group, we evaluated the effect of the administered ototoxic antibiotics. Timing of audiological control of the hearing organ condition are demonstrated for premature children after ototoxicosis, required methods of its examination are established.

Exposure to lead, mercury, styrene, and toluene and hearing impairment: evaluation of dose-response relationships, regulations, and controls.

The risk of hearing loss from exposure to ototoxic chemicals is not reflected in occupational exposure limits and most jurisdictions. The aims of this research were to investigate dose-response relationships between exposure to lead, mercury, toluene, and styrene and hearing impairment based on current epidemiological evidence, conduct cross-jurisdictional comparisons, and investigate control measures for exposure to ototoxic chemicals. Ovid Medline and Ovid Embase databases were used to find relevant publications. A total of 86 epidemiological studies met the eligibility criteria for final evaluation. When significant associations between exposure and outcome were identified, exposure levels were evaluated to determine whether No Observed Adverse Effect Level (NOAEL) and Lowest Observed Adverse Effect Level (LOAEL) could be identified. Cross-jurisdictional comparisons included the U.K., U.S., Canada, and Australia occupational health and safety legislations. The majority of lead (75%), styrene (74%), and toluene (77%) studies showed significantly increased risks of hearing loss from exposure to these substances, although numerous studies on toluene (70%) and styrene (16%) compared auditory function between "solvent mixture" or "noise and solvent mixture" exposed groups and controls and not necessarily on groups exposed to a single agent. Based on five studies, blood lead ranges of 1-1.99 µg/dL to 2.148-2.822 µg/dL were identified as NOAELs while blood lead levels of 2 µg/dL up to 2.823-26.507 µg/dL were identified as LOAELs for hearing loss. Except for general duty clauses, the U.S., Canadian, and Australian jurisdictions have set no enforceable regulations specific to ototoxic chemical exposures. A biological exposure index of 2 µg/dL is recommended for prevention of hearing impairment from lead exposure. Based on Safe Work Australia, noise exposure limits may be reduced to 80 dB(A) for 8 hr. Other recommendations include performing audiometric testing and controlling exposure through all routes of entry.

[Screening audiological control in children of different ages after taking ototoxic medications]. / Skriningovyi audiologicheskii kontrol' detei raznogo vozrasta posle priema ototoksicheskikh preparatov.

AIM: To compare auditory function during screening of children of different age groups who received ototoxic therapy. PATIENTS AND METHODS: Auditory function was studied in various categories of children receiving ototoxic drugs. Hearing was assessed by the registration of distortion product otoacoustic emission (DPOAE), short-latency evoked potentials (SLEP), tympanometry. Statistical processing was performed using the C program Statgraphics Centurion XV. RESULTS: In this study, screening of auditory function in children suffering from cystic fibrosis and receiving ototoxic treatment revealed pathologic conditions of the middle ear according to tympanometry in 15.4% of cases, impaired auditory function in 28.2% of cases according to DPOAE. Early ototoxicosis presented as a decrease in the amplitude of the response at a frequency of 4 kHz, and a change in the structure of the DP-gram in the form of a shift to the low-frequency area. Examination of the auditory function of premature infants receiving potentially ototoxic drugs in the early neonatal period demonstrated that the administration of ototoxic drugs does not affect the maturation of outer hair cells. CONCLUSION: Audiological control, such as tympanometry and registration of evoked otoacoustic remission should be included in the outpatient observation of children with a history of ototoxic drugs.

Why study inner ear hair cell mitochondria?

In several systems of the body (muscle, liver, nerves), new studies have examined the internal structure of mitochondria and brought to light striking new findings about how mitochondria are constructed and how their structure affects cell function. In the inner ear field, however, we have little structural knowledge about hair cell and supporting cell mitochondria, and virtually none about mitochondrial subtypes or how they function in health and disease. The need for such knowledge is discussed in this short review.

In vitro gentamicin exposure alters caveolae protein profile in cochlear spiral ligament pericytes.

BACKGROUND: The aminoglycoside antibiotic gentamicin is an ototoxic drug and has been used experimentally to investigate cochlear damage induced by noise.We have investigated the changes in the protein profile associated with caveolae in gentamicin treated and untreated spiral ligament (SL) pericytes, specialized cells in the blood labyrinth barrier of the inner ear microvasculature. Pericytes from various microvascular beds express caveolae, protein and cholesterol rich microdomains, which can undergo endocytosis and transcytosis to transport small molecules in and out the cells. A different protein profile in transport-specialized caveolae may induce pathological changes affecting the integrity of the blood labyrinth barrier and ultimately contributing to hearing loss. METHOD: Caveolae isolation from treated and untreated cells is achieved through ultracentrifugation of the lysates in discontinuous gradients. Mass spectrometry (LC-MS/MS) analysis identifies the proteins in the two groups. Proteins segregating with caveolae isolated from untreated SL pericytes are then compared to caveolae isolated from SL pericytes treated with the gentamicin for 24 h. Data are analyzed using bioinformatic tools. RESULTS: The caveolae proteome in gentamicin treated cells shows that 40% of total proteins are uniquely associated with caveolae during the treatment, and 15% of the proteins normally associated with caveolae in untreated cell are suppressed. Bioinformatic analysis of the data shows a decreased expression of proteins involved in genetic information processing, and an increase in proteins involved in metabolism, vesicular transport and signal transduction in gentamicin treated cells. Several Rab GTPases proteins, ubiquitous transporters, uniquely segregate with caveolae and are significantly enriched in gentamicin treated cells. CONCLUSION: We report that gentamicin exposure modifies protein profile of caveolae from SL pericytes. We identified a pool of proteins which are uniquely segregating with caveolae during the treatment, mainly participating in metabolic and biosynthetic pathways, in transport pathways and in genetic information processing. Finally, we show for the first time proteins associated with caveolae SL pericytes linked to nonsyndromic hearing loss.

Determining the prevalence of vestibular screening failures in pediatric cancer patients whose therapies include radiation to the head/neck and platin-based therapies: A pilot study.

BACKGROUND: Sensorineural hearing loss due to ototoxic cancer therapy is well established; effects on the vestibular system are unknown. We examined the feasibility of implementing vestibular screens for pediatric cancer survivors exposed to ototoxic agents. The prevalence of screening failures is reported. METHODS: Cancer survivors who were 6-17 years, at least 1-month posttreatment, and received ototoxic therapy (radiation to the head/neck, cisplatin, carboplatin) were eligible. Screening measures included (1) Pediatric Vestibular Symptom Questionnaire, (2) Modified Clinical Test of Sensory Interaction on Balance, and (3) Dynamic Visual Acuity. RESULTS: Vestibular screening failures were observed in 30 participants (60%). Patients with a brain tumor diagnosis were at increased risk for failures compared to nonbrain tumor patients (74.2% vs. 36.8%, P = 0.009). Patients who underwent brain surgery were at increased risk for failures compared to patients without brain surgery (71% vs. 42%, P = 0.043). Patients with a longer duration between end of treatment and vestibular screening had a reduced risk of failures, with an almost 20% decrease for each year between the time points (odds ratio = 0.812; 95% confidence interval: 0.683-0.964, P = 0.018). Receiving carboplatin correlated with a decreased risk of failure (P = 0.016), due to a negative correlation with other clinical risk factors (diagnosis of a brain tumor, major brain surgery) that are associated with vestibular screening failure. CONCLUSION: Vestibular screening failures are highly prevalent in childhood cancer survivors who received ototoxic therapy. Broad screening of this population and further characterization of these patients are warranted.

Current practice of ototoxicity management across the United Kingdom (UK).

OBJECTIVE: Effective management of patients diagnosed with ototoxicity is needed to reduce hearing and balance damage which affects communication and life quality. Despite widespread recommendations to monitor and manage ototoxicity in an early and effective manner, there is limited evidence to support the actual implementation of these recommendations for affected patient groups in healthcare services across the UK with limited publications available. In this study, an online questionnaire analysed the current practice of ototoxicity management and patient pathways across the UK once the diagnosis of ototoxicity was confirmed, targeting Audiologists, ENTs/AVPs and GPs. DESIGN: Qualitative Survey Study. STUDY SAMPLE: A randomised sample of hearing services in the UK, including audiology departments; GP practices and local health settings were targeted with a total of 134 completed surveys. RESULTS: About 72% reported the absence of ototoxicity management protocols within their centre. Results depicted great inconsistency and variation across the UK in ototoxicity management services provided, treatment modification, monitoring and referral pathways. CONCLUSION: Developing and advocating national guidelines are intended not only to inform clinical decision making but to provide minimum standards of care in ototoxicity management and offer greater awareness and education to improve patients' quality of life.

Susceptibility of linear and nonlinear otoacoustic emission components to low-dose styrene exposure.

OBJECTIVE: To investigate potential susceptibility of active cochlear mechanisms to low-level styrene exposure by comparing TEOAEs in workers and controls. DESIGN: Two advanced analysis techniques were applied to detect sub-clinical changes in linear and nonlinear cochlear mechanisms of OAE generation: the wavelet transform to decompose TEOAEs into time-frequency components and extract signal-to-noise ratio and latency of each component, and the bispectrum to detect and extract nonlinear TEOAE contributions as quadratic frequency couplings (QFCs). STUDY SAMPLE: Two cohorts of workers were examined: subjects exposed exclusively to styrene (N = 9), and subjects exposed to styrene and noise (N = 6). The control group was perfectly matched by age and sex to the exposed group. RESULTS: Exposed subjects showed significantly lowered SNR in TEOAE components at mid-to-high frequencies (above 1.6 kHz) and a shift of QFC distribution towards lower frequencies than controls. No systematic differences were observed in latency. CONCLUSION: Low-level styrene exposure may have induced a modification of cochlear functionality as concerns linear and nonlinear OAE generation mechanisms. The lack of change in latency seems to suggest that the OAE components, where generation region and latency are tightly coupled, may not have been affected by styrene and noise exposure levels considered here.

Drug screening identifies aldose reductase as a novel target for treating cisplatin-induced hearing loss.

Cisplatin is a frequently used chemotherapeutic medicine for cancer treatment. Permanent hearing loss is one of the most serious side effects of cisplatin, but there are few FDA-approved medicines to prevent it. We applied high-through screening and target fishing and identified aldose reductase, a key enzyme of the polyol pathway, as a novel target for treating cisplatin ototoxicity. Cisplatin treatment significantly increased the expression level and enzyme activity of aldose reductase in the cochlear sensory epithelium. Genetic knockdown or pharmacological inhibition of aldose reductase showed a significant protective effect on cochlear hair cells. Cisplatin-induced overactivation of aldose reductase led to the decrease of NADPH/NADP+ and GSH/GSSG ratios, as well as the increase of oxidative stress, and contributed to hair cell death. Results of target prediction, molecular docking, and enzyme activity detection further identified that Tiliroside was an effective inhibitor of aldose reductase. Tiliroside was proven to inhibit the enzymatic activity of aldose reductase via competitively interfering with the substrate-binding region. Both Tiliroside and another clinically approved aldose reductase inhibitor, Epalrestat, inhibited cisplatin-induced oxidative stress and subsequent cell death and thus protected hearing function. These findings discovered the role of aldose reductase in the pathogenesis of cisplatin-induced deafness and identified aldose reductase as a new target for the prevention and treatment of hearing loss.

Audiological Profile of a Rare Case with 1 kHz Notch Audiogram.

A notch is defined as the frequency point at which hearing loss is greater than 15 dB when compared to one octave above and below. C3 dip or 1 kHz notch is rarely seen and not much information is known about the clinical profile of such condition. The aim of this case report is to highlight the audiological profile of a case with 1kHz notch and discuss the possible causes for the same. Case A (16 yrs) was referred with a complaint of hearing loss and speech understanding difficulty specially at school. The teen had taken multiple medications for several health related issues like malaria, appendicitis and the understanding difficulty was evident during this period. Detailed audiological evaluation revealed a significant C3 dip in the right ear and normal hearing sensitivity in the left ear. Evidences from literature suggests strong correlation between drugs like Cefotetan, cefotaime, piperacillin, ampicillin (appendicitis treatment) and chloroquine (malaria) and hearing loss. Hence, we concluded that the possible cause of 1khz is ototoxic medication.

Ototoxicity-related changes in GABA immunolabeling within the rat inferior colliculus.

Several studies suggest that hearing loss results in changes in the balance between inhibition and excitation in the inferior colliculus (IC). The IC is an integral nucleus within the auditory brainstem. The majority of ascending pathways from the lateral lemniscus (LL), superior olivary complex (SOC), and cochlear nucleus (CN) synapse in the IC before projecting to the thalamus and cortex. Many of these ascending projections provide inhibitory innervation to neurons within the IC. However, the nature and the distribution of this inhibitory input have only been partially elucidated in the rat. The inhibitory neurotransmitter, gamma aminobutyric acid (GABA), from the ventral nucleus of the lateral lemniscus (VNLL), provides the primary inhibitory input to the IC of the rat with GABA from other lemniscal and SOC nuclei providing lesser, but prominent innervation. There is evidence that hearing related conditions can result in dysfunction of IC neurons. These changes may be mediated in part by changes in GABA inputs to IC neurons. We have previously used gene micro-arrays in a study of deafness-related changes in gene expression in the IC and found significant changes in GAD as well as the GABA transporters and GABA receptors (Holt 2005). This is consistent with reports of age and trauma related changes in GABA (Bledsoe et al., 1995; Mossop et al., 2000; Salvi et al., 2000). Ototoxic lesions of the cochlea produced a permanent threshold shift. The number, intensity, and density of GABA positive axon terminals in the IC were compared in normal hearing and deafened rats. While the number of GABA immunolabeled puncta was only minimally different between groups, the intensity of labeling was significantly reduced. The ultrastructural localization and distribution of labeling was also examined. In deafened animals, the number of immuno gold particles was reduced by 78 % in axodendritic and 82 % in axosomatic GABAergic puncta. The affected puncta were primarily associated with small IC neurons. These results suggest that reduced inhibition to IC neurons contribute to the increased neuronal excitability observed in the IC following noise or drug induced hearing loss. Whether these deafness diminished inhibitory inputs originate from intrinsic or extrinsic CNIC sources awaits further study.

Biosafety and potency of high-molecular-weight hyaluronic acid with intratympanic dexamethasone delivery for acute hearing loss.

Objective: This study evaluated the potential of high-molecular-weight hyaluronic acid (HHA) as an intratympanic (IT) drug delivery vehicle for dexamethasone (D) in treating acute hearing loss. We compared the efficacy, safety, and residence time of HHA to the standard-of-care IT drug delivery method. Methods: Endoscopic examinations were used to track tympanic membrane (TM) healing post-IT injection. Micro-computed tomography (CT) was used to gauge drug/vehicle persistence in the bulla air space. Histological analyses covered the middle ear, TM, and hair cell counts. Auditory brainstem responses (ABR) were used to measure hearing thresholds, while high-performance liquid chromatography (HPLC) was employed to quantify cochlear perilymph dexamethasone concentrations. Results: The HHA + D group had a notably prolonged drug/vehicle residence time in the bulla (41 ± 27 days) compared to the saline + D group (1.1 ± 0.3 days). Complete TM healing occurred without adverse effects. Histology revealed no significant intergroup differences or adverse outcomes. Hearing recovery trends favored the HHA + D group, with 85.0% of ears showing clinically meaningful improvement. D concentrations in cochlear perilymph were roughly double in the HHA group. Conclusion: HHA is a promising vehicle for IT drug delivery in treating acute hearing loss. It ensures extended residence time, augmented drug concentrations in targeted tissues, and safety. These results highlight the potential for HHA + D to excel beyond existing standard-of-care treatments for acute hearing loss.

Development of Chinese herbal medicine for sensorineural hearing loss.

According to the World Health Organization's world report on hearing, nearly 2.5 billion people worldwide will suffer from hearing loss by 2050, which may contribute to a severe impact on individual life quality and national economies. Sensorineural hearing loss (SNHL) occurs commonly as a result of noise exposure, aging, and ototoxic drugs, and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear, which is mainly triggered by reactive oxygen species accumulation, inflammation, and mitochondrial dysfunction. Though recent advances have been made in understanding the ability of cochlear repair and regeneration, there are still no effective therapeutic drugs for SNHL. Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine. Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL, and elucidate their molecular mechanisms of action, to pave the way for further research and development of novel effective drugs in this field.

Effect of melatonin on otoprotection in rodents: a systematic review with meta-analysis.

OBJECTIVES: To determinate the otoprotective efficacy of melatonin.in experimental models of rodents through a systematic review of the literature. METHODS: Altogether, 154 articles were found in four databases. The PICOS strategy (Population, Intervention, Comparison, and Outcome) was used to define the eligibility criteria. Studies that met the inclusion criteria for the second step were included in a qualitative synthesis. Each study type was analyzed with the CAMARADES quality of assessment's checklist and the SYRCLE RoBS risk of bias. RESULTS: Seven articles were selected, and four were included in the meta-analysis. It was possible to obtain seven outcomes according to the standard auditory frequencies presented among the studies, considering a minimum of three standard frequencies. The outcomes analyzed were for the frequencies of 1500, 2000, 3000, 4000, 5000, 6000, and 8000 Hz. CONCLUSION: Melatonin can provide protection against the ototoxic effects of cisplatin and aminoglycosides at 5000 Hz, 6000 Hz, and 8000 Hz, thereby minimizing the reduction in Otoacustic Emissions (OAE) amplitude. The same effect was not observed in the lower frequencies. Despite the limited number of studies that were evaluated, the results appeared consistent in higher frequencies. However, the methodology of the available studies did not meet the necessary methodological rigor that promotes the safe replicability of these studies.

Topical gentamicin-induced acute vestibulopathy: A case report.

Evidence suggests that otologic injury from ototopical aminoglycoside preparations is infrequent when used to treat ear infections with an intact tympanic membrane. Meanwhile, parenteral administration of aminoglycosides, is well known to be associated with a significant incidence of cochlear and vestibular damage. The discrepancy between topical and parenteral ototoxic effects is thought to result from a combination of factors, including the protective function of debris overlying the round window membrane, low antibiotic concentrations of topical antibiotic preparations, length of exposure and inability to detect subtle hearing or vestibular changes. Herein, we present a case of acute vestibulopathy following a 2-week course of topical gentamicin otic drops. Awareness of vestibulotoxicity following topical gentamicin therapy is prudent as vestibulopathic symptoms can be severely debilitating.

Cabazitaxel's ototoxicity: An animal study and histopathologic research.

Introduction: Chemotherapeutic agents can have both serious side effects and ototoxicity, which can be caused by direct toxic effects or by metabolic derangement by the agents. Cabazitaxel (CBZ) is a next-generation semi-synthetic taxane derivative that is effective in both preclinical models of human tumors that are sensitive or resistant to chemotherapy and in patients suffering from progressive prostate cancer despite docetaxel treatment. The primary aim of this study is to investigate the ototoxicity of CBZ in a rat model. Materials and Methods: : A total of 24 adult male Wistar-Albino rats were equally and randomly divided into four groups. CBZ (Jevtana, Sanofi-Aventis USA) was intraperitoneally administered to Groups 2, 3, and 4 at doses of 0.5, 1.0, and 1.5 mg/kg/week, respectively, for 4 consecutive weeks; Group 1 received only i.p. saline at the same time. At the end of the study, the animals were sacrificed and their cochlea removed for histopathological examination. Results: : Intraperitoneal administration of CBZ exerted an ototoxic effect on rats, and the histopathological results became worse in a dose-dependent manner (P < 0.05). Conclusion: : Our findings suggest that CBZ may be an ototoxic agent and can damage the cochlea. More clinical studies should be conducted to understand its ototoxicity.