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Otolaryngologic Clinics of North America Dec 2021Ototoxicity refers to damage to the inner ear that leads to functional hearing loss or vestibular disorders by selected pharmacotherapeutics as well as a variety of... (Review)
Review
Ototoxicity refers to damage to the inner ear that leads to functional hearing loss or vestibular disorders by selected pharmacotherapeutics as well as a variety of environmental exposures (eg, lead, cadmium, solvents). This article reviews the fundamental mechanisms underlying ototoxicity by clinically relevant, hospital-prescribed medications (ie, aminoglycoside antibiotics or cisplatin, as illustrative examples). Also reviewed are current strategies to prevent prescribed medication-induced ototoxicity, with several clinical or candidate interventional strategies being discussed.
Topics: Aminoglycosides; Anti-Bacterial Agents; Cisplatin; Ear, Inner; Humans; Ototoxicity
PubMed: 34774227
DOI: 10.1016/j.otc.2021.08.007 -
The Lancet. Child & Adolescent Health Feb 2020Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse... (Review)
Review
Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse event. To develop a clinical practice guideline for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer, we convened an international, multidisciplinary panel of experts and patient advocates to update a systematic review of randomised trials for the prevention of cisplatin-induced ototoxicity. The systematic review identified 27 eligible adult and paediatric trials that evaluated amifostine, sodium diethyldithiocarbamate or disulfiram, systemic sodium thiosulfate, intratympanic therapies, and cisplatin infusion duration. Regarding systemic sodium thiosulfate, the panel made a strong recommendation for administration in non-metastatic hepatoblastoma, a weak recommendation for administration in other non-metastatic cancers, and a weak recommendation against its routine use in metastatic cancers. Amifostine, sodium diethyldithiocarbamate, and intratympanic therapy should not be routinely used. Cisplatin infusion duration should not be altered as a means to reduce ototoxicity. Further research to determine the safety of sodium thiosulfate in patients with metastatic cancer is encouraged.
Topics: Adolescent; Antineoplastic Agents; Child; Cisplatin; Female; Hearing Loss; Humans; Male; Neoplasms; Ototoxicity; Prognosis; Randomized Controlled Trials as Topic; Survival Rate; Thiosulfates
PubMed: 31866182
DOI: 10.1016/S2352-4642(19)30336-0 -
Biomedicine & Pharmacotherapy =... Jan 2023Administration of cisplatin, a common chemotherapeutic drug, has an inevitable side effect of sensorineural hearing loss. The main etiologies are stria vascularis... (Review)
Review
Administration of cisplatin, a common chemotherapeutic drug, has an inevitable side effect of sensorineural hearing loss. The main etiologies are stria vascularis injury, spiral ganglion degeneration, and hair cell death. Over several decades, the research scope of cisplatin-induced ototoxicity has expanded with the discovery of the molecular mechanism mediating inner ear cell death, highlighting the roles of reactive oxygen species and transport channels for cisplatin uptake into inner ear cells. Upon entering hair cells, cisplatin disrupts organelle metabolism, induces oxidative stress, and targets DNA to cause intracellular damage. Recent studies have also reported the role of inflammation in cisplatin-induced ototoxicity. In this article, we preform a narrative review of the latest reported molecular mechanisms of cisplatin-induced ototoxicity, from extracellular to intracellular. We build up a signaling network starting with cisplatin entering into the inner ear through the blood labyrinth barrier, disrupting cochlear endolymph homeostasis, and activating inflammatory responses of the outer hair cells. After entering the hair cells, cisplatin causes hair cell death via DNA damage, redox system imbalance, and mitochondrial and endoplasmic reticulum dysfunction, culminating in programmed cell death including apoptosis, necroptosis, autophagic death, pyroptosis, and ferroptosis. Based on the mentioned mechanisms, prominent therapeutic targets, such as channel-blocking drugs of cisplatin transporter, construction of cisplatin structural analogues, anti-inflammatory drugs, antioxidants, cell death inhibitors, and others, were collated. Considering the recent research efforts, we have analyzed the feasibility of the aforementioned therapeutic strategies and proposed our otoprotective approaches to overcome cisplatin-induced ototoxicity.
Topics: Humans; Cisplatin; Antineoplastic Agents; Hair Cells, Auditory; Ototoxicity; Cochlea; Apoptosis
PubMed: 36455457
DOI: 10.1016/j.biopha.2022.114045 -
Frontiers in Cellular Neuroscience 2023Mitochondrial dysfunction is associated with ototoxicity, which is caused by external factors. Mitophagy plays a key role in maintaining mitochondrial homeostasis and... (Review)
Review
Mitochondrial dysfunction is associated with ototoxicity, which is caused by external factors. Mitophagy plays a key role in maintaining mitochondrial homeostasis and function and is regulated by a series of key mitophagy regulatory proteins and signaling pathways. The results of ototoxicity models indicate the importance of this process in the etiology of ototoxicity. A number of recent investigations of the control of cell fate by mitophagy have enhanced our understanding of the mechanisms by which mitophagy regulates ototoxicity and other hearing-related diseases, providing opportunities for targeting mitochondria to treat ototoxicity.
PubMed: 36909283
DOI: 10.3389/fncel.2023.1140916 -
Journal of Cellular and Molecular... Oct 2020Ferroptosis is a recently recognized form of non-apoptotic cell death caused by an iron-dependent accumulation of lipid hydroperoxides, which plays important roles in a...
Ferroptosis is a recently recognized form of non-apoptotic cell death caused by an iron-dependent accumulation of lipid hydroperoxides, which plays important roles in a wide spectrum of pathological conditions. The present study was aimed to investigate the impact of ferroptosis on cisplatin-induced sensory hair cell damage. Cell viability was determined by Cell Counting Kit-8 and lactase dehydrogenase assays. The reactive oxygen species (ROS) levels were evaluated by 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA) and MitoSox-Red staining. Mitochondrial membrane potential (MMP) was measured by tetramethylrhodamine methyl ester (TMRM) staining. Lipid peroxidation, intracellular and mitochondrial iron were detected by Liperfluo, C11-BODIPY , FerroOrange and Mito-FerroGreen, respectively. We found that cisplatin treatment not only markedly augmented ROS accumulation, decreased the MMP, but increased lipid peroxidation and iron accumulation in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. Of note, treatment with the specific ferroptosis inhibitor ferrostatin-1 could effectively abrogate the cisplatin-induced toxicity and subsequent cell death. Specifically, the improvement of mitochondrial functions is important mechanisms for protective action of ferroptosis inhibitor against cisplatin-induced damages in HEI-OC1 cells. Moreover, inhibition of ferroptosis significantly protected murine cochlear hair cells against cisplatin damage. In addition, treatment murine cochlear hair cells with ferroptosis inducer, RSL3, significantly exacerbated cisplatin-induced damage, which could be alleviated by ROS inhibitor N-acetyl-L-cysteine. Collectively, our study indicated that ferroptosis inhibition could alleviate the cisplatin-induced ototoxicity via inactivation of lipid peroxide radical and improvement of mitochondrial function in hair cells.
Topics: Aldehydes; Animals; Carbolines; Cell Line; Cell Survival; Cisplatin; Cyclohexylamines; Cytoprotection; Ferroptosis; Hair Cells, Auditory; Iron; Iron Overload; Membrane Potential, Mitochondrial; Mice, Inbred C57BL; Ototoxicity; Phenylenediamines; Reactive Oxygen Species
PubMed: 32929878
DOI: 10.1111/jcmm.15839 -
Journal of Cystic Fibrosis : Official... Jan 2021
Topics: Aminoglycosides; Anti-Bacterial Agents; Cystic Fibrosis; Humans; Ototoxicity
PubMed: 33526212
DOI: 10.1016/j.jcf.2021.01.003 -
Frontiers in Neurology 2021It is well-known that aminoglycoside antibiotics can cause significant hearing loss and vestibular deficits that have been described in animal studies and in clinical... (Review)
Review
It is well-known that aminoglycoside antibiotics can cause significant hearing loss and vestibular deficits that have been described in animal studies and in clinical reports. The purpose of this review is to summarize relevant preclinical and clinical publications that discuss the ototoxicity of non-aminoglycoside antibiotics. The major classes of antibiotics other than aminoglycosides that have been associated with hearing loss in animal studies and in patients are discussed in this report. These antibiotics include: capreomycin, a polypeptide antibiotic that has been used to treat patients with drug-resistant tuberculosis, particularly in developing nations; the macrolides, including erythromycin, azithromycin and clarithromycin; and vancomycin. These antibiotics have been associated with ototoxicity, particularly in neonates. It is critical to be aware of the ototoxic potential of these antibiotics since so much attention has been given to the ototoxicity of aminoglycoside antibiotics in the literature.
PubMed: 33767665
DOI: 10.3389/fneur.2021.652674 -
Cancer Jun 2016Ototoxicity is a well-established toxicity associated with a subgroup of antineoplastic therapies that includes platinum chemotherapy, radiation or surgery involving the... (Review)
Review
Ototoxicity is a well-established toxicity associated with a subgroup of antineoplastic therapies that includes platinum chemotherapy, radiation or surgery involving the ear and auditory nerve, and supportive care agents such as aminoglycoside antibiotics and loop diuretics. The reported prevalence of ototoxicity in patients who have received potentially ototoxic therapy ranges from 4% to 90% depending on factors such as age of the patient population, agent(s) used, cumulative dose, and administration techniques. The impact of ototoxicity on subsequent health-related and psychosocial outcomes in these patients can be substantial, and the burden of morbidity related to ototoxic agents is particularly high in very young children. Considerable interindividual variability in the prevalence and severity of ototoxicity has been observed among patients receiving similar treatment, suggesting genetic susceptibility as a risk factor. The development and testing of otoprotective agents is ongoing; however, to the author's knowledge, no US Food and Drug Administration-approved otoprotectants are currently available. Prospective monitoring for ototoxicity allows for comparison of auditory outcomes across clinical trials, as well as for early detection, potential alterations in therapy, and auditory intervention and rehabilitation to ameliorate the adverse consequences of hearing loss. Cancer 2016;122:1647-58. © 2016 American Cancer Society.
Topics: Age Factors; Antineoplastic Agents; Ear; Ear Diseases; Genetic Predisposition to Disease; Hearing Loss; Humans; Medical Illustration; Neoplasms; Postoperative Complications; Prevalence; Radiation Injuries; Radiotherapy; Tinnitus; Vertigo
PubMed: 26859792
DOI: 10.1002/cncr.29779 -
International Journal of Audiology Sep 2018Neonates admitted to the neonatal intensive care unit (NICU) are at greater risk of permanent hearing loss compared to infants in well mother and baby units. Several... (Review)
Review
OBJECTIVES
Neonates admitted to the neonatal intensive care unit (NICU) are at greater risk of permanent hearing loss compared to infants in well mother and baby units. Several factors have been associated with this increased prevalence of hearing loss, including congenital infections (e.g. cytomegalovirus or syphilis), ototoxic drugs (such as aminoglycoside or glycopeptide antibiotics), low birth weight, hypoxia and length of stay. The aetiology of this increased prevalence of hearing loss remains poorly understood.
DESIGN
Here we review current practice and discuss the feasibility of designing improved ototoxicity screening and monitoring protocols to better identify acquired, drug-induced hearing loss in NICU neonates.
STUDY SAMPLE
A review of published literature.
CONCLUSIONS
We conclude that current audiological screening or monitoring protocols for neonates are not designed to adequately detect early onset of ototoxicity. This paper offers a detailed review of evidence-based research, and offers recommendations for developing and implementing an ototoxicity monitoring protocol for young infants, before and after discharge from the hospital.
Topics: Age Factors; Child, Preschool; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Early Diagnosis; Hearing; Hearing Loss; Hearing Tests; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Predictive Value of Tests; Risk Assessment; Risk Factors
PubMed: 28949262
DOI: 10.1080/14992027.2017.1339130 -
Cancer Jan 2022Platinum-containing chemotherapy is often used to treat children with cancer. Although it is a very effective medication, unfortunately, it causes permanent hearing loss...
Platinum-containing chemotherapy is often used to treat children with cancer. Although it is a very effective medication, unfortunately, it causes permanent hearing loss in more than one-half of the children who receive it. In this issue of Cancer, an article by Meijer and colleagues shows that very young children are affected early on in their treatment and suggests that the younger the child the more frequently their hearing should be tested during treatment. This proposal is a real challenge for oncology centers and families practically, emotionally, and socioeconomically. The findings are provocative but equally stimulating and encouraging; hopefully, they will lead to a new standard of multidisciplinary care for children receiving platinum chemotherapy.
Topics: Antineoplastic Agents; Carboplatin; Child; Child, Preschool; Cisplatin; Hearing Loss; Humans; Ototoxicity
PubMed: 34490622
DOI: 10.1002/cncr.33847