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Frontiers in Neurology 2022The inner ear can be insulted by various noxious stimuli, including drugs (cisplatin and aminoglycosides) and over-acoustic stimulation. These stimuli damage the hair... (Review)
Review
The inner ear can be insulted by various noxious stimuli, including drugs (cisplatin and aminoglycosides) and over-acoustic stimulation. These stimuli damage the hair cells giving rise to progressive hearing loss. Systemic drugs have attempted protection from ototoxicity. Most of these drugs poorly reach the inner ear with consequent ineffective action on hearing. The reason for these failures resides in the poor inner ear blood supply, the presence of the blood-labyrinthine barrier, and the low permeability of the round window membrane (RWM). This article presents a review of the use of nanoparticles (NPs) in otoprotection. NPs were recently used in many fields of medicine because of their ability to deliver drugs to the target organs or cells. The studies included in the review regarded the biocompatibility of the used NPs by and experiments. In most studies, NPs proved safe without a significant decrease in cell viability or signs of ototoxicity. Many nano-techniques were used to improve the drugs' kinetics and efficiency. These techniques included encapsulation, polymerization, surface functionalization, and enhanced drug release. In such a way, it improved drug transmission through the RWM with increased and prolonged intra-cochlear drug concentrations. In all studies, the fabricated drug-NPs effectively preserved the hair cells and the functioning hearing from exposure to different ototoxic stimuli, simulating the actual clinical circumstances. Most of these studies regarded cisplatin ototoxicity due to the wide use of this drug in clinical oncology. Dexamethasone (DEX) and antioxidants represent the most used drugs in most studies. These drugs effectively prevented apoptosis and reactive oxygen species (ROS) production caused by ototoxic stimuli. These various successful experiments confirmed the biocompatibility of different NPs and made it successfully to human clinical trials.
PubMed: 35968304
DOI: 10.3389/fneur.2022.912647 -
Molecular and Cellular Neurosciences May 2022Aminoglycosides are potent antibiotics that are commonly prescribed worldwide. Their use carries significant risks of ototoxicity by directly causing inner ear hair cell... (Review)
Review
Aminoglycosides are potent antibiotics that are commonly prescribed worldwide. Their use carries significant risks of ototoxicity by directly causing inner ear hair cell degeneration. Despite their ototoxic side effects, there are currently no approved antidotes. Here we review recent advances in our understanding of aminoglycoside ototoxicity, mechanisms of drug transport, and promising sites for intervention to prevent ototoxicity.
Topics: Aminoglycosides; Anti-Bacterial Agents; Humans; Ototoxicity
PubMed: 35341941
DOI: 10.1016/j.mcn.2022.103722 -
International Journal of Molecular... Nov 2023Cisplatin is a commonly used chemotherapeutic agent with proven efficacy in treating various malignancies, including testicular, ovarian, cervical, breast, bladder, head... (Review)
Review
Cisplatin is a commonly used chemotherapeutic agent with proven efficacy in treating various malignancies, including testicular, ovarian, cervical, breast, bladder, head and neck, and lung cancer. Cisplatin is also used to treat tumors in children, such as neuroblastoma, osteosarcoma, and hepatoblastoma. However, its clinical use is limited by severe side effects, including ototoxicity, nephrotoxicity, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, and retinal toxicity. Cisplatin-induced ototoxicity manifests as irreversible, bilateral, high-frequency sensorineural hearing loss in 40-60% of adults and in up to 60% of children. Hearing loss can lead to social isolation, depression, and cognitive decline in adults, and speech and language developmental delays in children. Cisplatin causes hair cell death by forming DNA adducts, mitochondrial dysfunction, oxidative stress, and inflammation, culminating in programmed cell death by apoptosis, necroptosis, pyroptosis, or ferroptosis. Contemporary medical interventions for cisplatin ototoxicity are limited to prosthetic devices, such as hearing aids, but these have significant limitations because the cochlea remains damaged. Recently, the U.S. Food and Drug Administration (FDA) approved the first therapy, sodium thiosulfate, to prevent cisplatin-induced hearing loss in pediatric patients with localized, non-metastatic solid tumors. Other pharmacological treatments for cisplatin ototoxicity are in various stages of preclinical and clinical development. This narrative review aims to highlight the molecular mechanisms involved in cisplatin-induced ototoxicity, focusing on cochlear inflammation, and shed light on potential antioxidant and anti-inflammatory therapeutic interventions to prevent or mitigate the ototoxic effects of cisplatin. We conducted a comprehensive literature search (Google Scholar, PubMed) focusing on publications in the last five years.
Topics: Humans; Child; Cisplatin; Antineoplastic Agents; Ototoxicity; Hearing Loss; Osteosarcoma; Deafness; Bone Neoplasms; Inflammation
PubMed: 38003734
DOI: 10.3390/ijms242216545 -
American Journal of Audiology Oct 2021Purpose This review article summarizes our current understanding of the mechanisms underlying acquired hearing loss from hospital-prescribed medications that affects as... (Review)
Review
Purpose This review article summarizes our current understanding of the mechanisms underlying acquired hearing loss from hospital-prescribed medications that affects as many as 1 million people each year in Western Europe and North America. Yet, there are currently no federally approved drugs to prevent or treat the debilitating and permanent hearing loss caused by the life-saving platinum-based anticancer drugs or the bactericidal aminoglycoside antibiotics. Hearing loss has long-term impacts on quality-of-life measures, especially in young children and older adults. This review article also highlights some of the current knowledge gaps regarding iatrogenic causes of hearing loss. Conclusion Further research is urgently needed to further refine clinical practice and better ameliorate iatrogenic drug-induced hearing loss.
Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Antineoplastic Agents; Child; Child, Preschool; Cisplatin; Humans; Ototoxicity
PubMed: 34415784
DOI: 10.1044/2021_AJA-21-00006 -
Pharmaceuticals (Basel, Switzerland) May 2022Nitrative stress is increasingly recognized as a critical mediator of apoptotic cell death in many pathological conditions. The accumulation of nitric oxide along with... (Review)
Review
Nitrative stress is increasingly recognized as a critical mediator of apoptotic cell death in many pathological conditions. The accumulation of nitric oxide along with superoxide radicals leads to the generation of peroxynitrite that can eventually result in the nitration of susceptible proteins. Nitrotyrosine is widely used as a biomarker of nitrative stress and indicates oxidative damage to proteins. Ototoxic insults, such as exposure to noise and ototoxic drugs, enhance the generation of 3-nitrotyrosine in different cell types in the cochlea. Nitrated proteins can disrupt critical signaling pathways and eventually lead to apoptosis and loss of sensory receptor cells in the cochlea. Accumulating evidence shows that selective targeting of nitrative stress attenuates cellular damage. Anti-nitrative compounds, such as peroxynitrite decomposition catalysts and inducible nitric oxide synthase inhibitors, prevent nitrative stress-mediated auditory damage. However, the role of nitrative stress in acquired hearing loss and its potential significance as a promising interventional target is yet to be fully characterized. This review provides an overview of nitrative stress mechanisms, the induction of nitrative stress in the auditory tissue after ototoxic insults, and the therapeutic value of targeting nitrative stress for mitigating auditory dysfunction.
PubMed: 35745568
DOI: 10.3390/ph15060649 -
Otolaryngologic Clinics of North America Aug 2020Tinnitus is commonly referred to as "ringing in the ears." Epidemiologic studies highlight challenges associated with clinical determination of tinnitus and... (Review)
Review
Tinnitus is commonly referred to as "ringing in the ears." Epidemiologic studies highlight challenges associated with clinical determination of tinnitus and ascertainment of its etiology, functional effects, temporal characteristics, psychoacoustic parameters, and risk factors. Because no standards exist for capturing these factors as measures, direct comparison of data between studies is not possible. This report suggests terminology and definitions to promote standardization, with a brief overview of findings from selected population-based epidemiologic studies. Tinnitus-specific data are presented from the Noise Outcomes in Servicemembers Epidemiology study. Further epidemiologic studies are needed to develop tinnitus treatment and a cure for this chronic condition.
Topics: Hearing Loss; Humans; Noise; Ototoxicity; Psychoacoustics; Risk Factors; Tinnitus
PubMed: 32362561
DOI: 10.1016/j.otc.2020.03.002 -
Laryngoscope Investigative... Aug 2021This study investigates the histopathological changes of the cochlea and vestibular end organs of a patient who received cisplatin for Hodgkin's lymphoma. He experienced...
This study investigates the histopathological changes of the cochlea and vestibular end organs of a patient who received cisplatin for Hodgkin's lymphoma. He experienced acute high-frequency sensorineural hearing loss and tinnitus after receiving treatment. Using histopathological analysis of his temporal bones after he unfortunately succumbed to his disease, we found that the ototoxic effect of cisplatin is primarily within the cochlea, with significant damage located at the organ of Corti at the base-hook region, consistent with findings in animal models. The effects of cisplatin were minimal when reviewing the vestibular end organs.
PubMed: 34401512
DOI: 10.1002/lio2.608 -
Otolaryngologic Clinics of North America Oct 2021Initial diagnosis of peripheral vestibulopathy requires a detailed history, physical examination, and, in some cases, audiovestibular testing, radiographic imaging, or... (Review)
Review
Initial diagnosis of peripheral vestibulopathy requires a detailed history, physical examination, and, in some cases, audiovestibular testing, radiographic imaging, or serology. Differentiation of a peripheral vestibulopathy as progressive or degenerative is often nuanced and influenced by a characterization of a patient's symptoms or natural history over time. A diverse group of vestibular pathology may fit into this category, including Ménière's disease, autoimmune conditions, congenital pathologies, ototoxic medications, radiation therapy, and perilymphatic fistula. Differentiation among these entities may be guided by initial or subsequent symptomatology, with various combinations of audiovestibular testing, serology, and imaging. Treatment options are disparate and disease-specific, ranging from observation to medical management or surgical intervention, underscoring the need for astute investigation and diagnosis.
Topics: Autoimmune Diseases; Humans; Meniere Disease; Radiography
PubMed: 34301401
DOI: 10.1016/j.otc.2021.05.015 -
Radiation Oncology (London, England) Jun 2023The risk of ototoxicity, characterized by hearing impairment, tinnitus, or middle ear inflammation, is elevated in both child and adult cancer survivors who have...
BACKGROUND
The risk of ototoxicity, characterized by hearing impairment, tinnitus, or middle ear inflammation, is elevated in both child and adult cancer survivors who have undergone head-neck or brain radiation, or a combination of the two. To provide optimal care for these cancer survivors and minimize subsequent complications, it is crucial to comprehend the relationship between radiotherapy and ototoxicity.
METHODS
A comprehensive search of databases, including the Cochrane Library, PubMed, Embase, and Web of Science, was conducted from the inception of the knowledge base up until January 2023. The metafor-package was employed to compare ototoxicity rates in individuals receiving radiotherapy. Two independent assessors extracted data and analyzed targets using a random-effects model.
RESULTS
Out of the 28 randomized controlled trials (RCTs) included in the analysis, 25 were prospective RCTs. Subgroup analysis revealed that mean cochlear radiation dose, primary tumor location, radiotherapy modality, and patient age significantly influenced total hearing impairment. Intensity-modulated radiotherapy was associated with less ototoxicity than 2D conventional radiotherapy (OR, 0.53; 95% CI, 0.47-0.60; P = 0.73; I = 0%). Stereotactic radiotherapy appeared to be a superior option for hearing preservation compared to radiosurgery (OR, 1.44; 95% CI, 1.00-2.07; P = 0.69; I = 0%). Children demonstrated a higher risk of hearing impairment than adults. More than 50% of patients with vestibular neuroadenoma experienced hearing impairment following radiation therapy. A strong association was observed between the average cochlear radiation dose and hearing impairment. Increased cochlear radiation doses may result in a heightened risk of hearing impairment.
CONCLUSION
Several risk factors for radiation-induced hearing impairment were identified in this study. High cochlear radiation doses were found to exacerbate the risk of hearing impairment resulting from radiation therapy.
Topics: Adult; Child; Humans; Hearing; Hearing Loss; Ototoxicity; Radiosurgery; Radiotherapy; Radiotherapy, Intensity-Modulated
PubMed: 37270526
DOI: 10.1186/s13014-023-02268-7 -
Paediatric Drugs Mar 2023Sodium thiosulfate (Pedmark) is a chemoprotectant/antioxidant developed by Fennec Pharmaceuticals (formerly Adherex Technologies) to reduce to risk of hearing loss... (Review)
Review
Sodium thiosulfate (Pedmark) is a chemoprotectant/antioxidant developed by Fennec Pharmaceuticals (formerly Adherex Technologies) to reduce to risk of hearing loss associated with cisplatin. Sodium thiosulfate reduces the risk of ototoxicity by interacting directly with cisplatin to produce inactive platinum species, as well as by causing intracellular effects (such as increasing antioxidant glutathione levels and inhibition of oxidative stress) after entering the cells through the sodium sulfate cotransporter 2. In September 2022, sodium thiosulfate received its first approval in the USA for reducing the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumours. Sodium thiosulfate is under regulatory review in the EU for the prevention of ototoxicity induced by cisplatin chemotherapy in patients 1 month to < 18 years of age with localised, non-metastatic, solid tumours. This article summarizes the milestones in the development of sodium thiosulfate leading to this pediatric first approval for reducing the risk of ototoxicity associated with cisplatin in pediatric patients.
Topics: Humans; Child; Cisplatin; Antineoplastic Agents; Antioxidants; Ototoxicity; Neoplasms
PubMed: 36517667
DOI: 10.1007/s40272-022-00550-x