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Therapie 2024Sensorineural hearing loss (SNHL) is the most common type of hearing loss. Causes include degenerative changes in the sensory hair cells, their synapses and/or the... (Review)
Review
Sensorineural hearing loss (SNHL) is the most common type of hearing loss. Causes include degenerative changes in the sensory hair cells, their synapses and/or the cochlear nerve. As human inner ear hair cells have no capacity for regeneration, their destruction is irreversible and leads to permanent hearing loss. SNHL can be genetically inherited or acquired through ageing, exposure to noise or ototoxic drugs. Ototoxicity generally refers to damage to the structures and functions of the inner ear following exposure to specific drugs. Ototoxicity can be multifactorial, causing damage to cochlear hair cells or cells with homeostatic functions that modulate cochlear hair cell function. Clinical strategies to limit ototoxicity include identifying patients at risk, monitoring drug concentrations, performing serial hearing assessments and switching to less ototoxic therapy. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the PubMed® database. The search terms "ototoxicity", "hearing loss" and "drugs" were combined. We included studies published between September 2013 and June 2023, and focused on medicines and drugs used in hospitals. The review highlighted a number of articles reporting the main drug classes potentially involved: namely, immunosuppressants, antimalarials, vaccines, antibiotics, antineoplastic agents, diuretics, nonsteroidal anti-inflammatory drugs and analgesics. The presumed ototoxic mechanisms were described, together with the therapeutic and preventive options developed over the last ten years.
Topics: Humans; Cochlea; Ototoxicity; Hearing Loss; Anti-Bacterial Agents
PubMed: 37957052
DOI: 10.1016/j.therap.2023.10.011 -
Molecules (Basel, Switzerland) Oct 2019In this study, we investigated whether the curcuminoids, CLEFMA and EF24, improved cisplatin efficacy and reduced cisplatin ototoxicity. We used the lung cancer cell...
In this study, we investigated whether the curcuminoids, CLEFMA and EF24, improved cisplatin efficacy and reduced cisplatin ototoxicity. We used the lung cancer cell line, A549, to determine the effects of the curcuminoids and cisplatin on cell viability and several apoptotic signaling mechanisms. Cellular viability was measured using the MTT assay. A scratch assay was used to measure cell migration and fluorescent spectrophotometry to measure reactive oxygen species (ROS) production. Western blots and luminescence assays were used to measure the expression and activity of apoptosis-inducing factor (AIF), caspases-3/7, -8, -9, and -12, c-Jun N-terminal kinases (JNK), mitogen-activated protein kinase (MAPK), and proto-oncogene tyrosine-protein kinase (Src). A zebrafish model was used to evaluate auditory effects. Cisplatin, the curcuminoids, and their combinations had similar effects on cell viability (IC values: 2-16 μM) and AIF, caspase-12, JNK, MAPK, and Src expression, while caspase-3/7, -8, and -9 activity was unchanged or decreased. Cisplatin increased ROS yield (1.2-fold), and curcuminoid and combination treatments reduced ROS (0.75-0.85-fold). Combination treatments reduced A549 migration (0.51-0.53-fold). Both curcuminoids reduced auditory threshold shifts induced by cisplatin. In summary, cisplatin and the curcuminoids might cause cell death through AIF and caspase-12. The curcuminoids may potentiate cisplatin's effect against A549 migration, but may counteract cisplatin's effect to increase ROS production. The curcuminoids might also prevent cisplatin ototoxicity.
Topics: A549 Cells; Animals; Antineoplastic Agents; Benzylidene Compounds; Caspases; Cell Death; Cisplatin; Diarylheptanoids; Evoked Potentials, Auditory; Humans; Inhibitory Concentration 50; Ototoxicity; Piperidones; Proto-Oncogene Mas; Zebrafish
PubMed: 31671767
DOI: 10.3390/molecules24213889 -
Frontiers in Neuroscience 2022Cisplatin is a known ototoxic chemotherapy drug, causing irreversible hearing loss. Evidence has shown that cisplatin causes inner ear damage as a result of adduct... (Review)
Review
Cisplatin is a known ototoxic chemotherapy drug, causing irreversible hearing loss. Evidence has shown that cisplatin causes inner ear damage as a result of adduct formation, a proinflammatory environment and the generation of reactive oxygen species within the inner ear. The main cochlear targets for cisplatin are commonly known to be the outer hair cells, the stria vascularis and the spiral ganglion neurons. Further evidence has shown that certain transporters can mediate cisplatin influx into the inner ear cells including organic cation transporter 2 (OCT2) and the copper transporter Ctr1. However, the expression profiles for these transporters within inner ear cells are not consistent in the literature, and expression of OCT2 and Ctr1 has also been observed in supporting cells. Organ of Corti supporting cells are essential for hair cell activity and survival. Special interest has been devoted to gap junction expression by these cells as certain mutations have been linked to hearing loss. Interestingly, cisplatin appears to affect connexin expression in the inner ear. While investigations regarding cisplatin-induced hearing loss have been focused mainly on the known targets previously mentioned, the role of supporting cells for cisplatin-induced ototoxicity has been overlooked. In this mini review, we discuss the implications of supporting cells expressing OCT2 and Ctr1 as well as the potential role of gap junctions in cisplatin-induced cytotoxicity.
PubMed: 35573297
DOI: 10.3389/fnins.2022.867034 -
Turkish Archives of Otorhinolaryngology Jun 2023Cisplatin is a chemotherapeutic agent with an ototoxic effect that is frequently used in head and neck cancers. There are studies in the literature conducted with...
OBJECTIVE
Cisplatin is a chemotherapeutic agent with an ototoxic effect that is frequently used in head and neck cancers. There are studies in the literature conducted with various antioxidant substances to protect and/or prevent ototoxicity. This study aims to investigate whether platelet-rich plasma (PRP) has a protective and therapeutic effect on cisplatin ototoxicity.
METHODS
A total of 40 Sprague Dawley albino rats were divided into six groups as control group (n=6), PRP-only group (n=6), cisplatin group (n=6), cisplatin + PRP group (n=6), PRP + cisplatin group (n=6), and donor group (n=10). At the beginning of the study and the 8 day, they were tested with distortion product otoacoustic emission (DPOAE). Assessment of DPOAE results was based on the signal-to-noise ratio in 2000, 3000, 4000, 6000, and 8000 Hz frequency bands. On the 8 day, the rats were sacrificed. For histological examinations, the temporal bones were dissected and fixed. After hematoxylin and eosin staining, the tissues were evaluated by light microscopy.
RESULTS
In the DPOAE tests performed on the 0 and 8 days of the cisplatin group, it was observed that cisplatin caused hearing loss in the rat ears. It was determined that the cisplatin group at 2000 Hz, 3000 Hz and 4000 Hz had a significant decrease in hearing compared to all groups (p<0.015), while the cisplatin group at 6000 and 8000 Hz was characterized by hearing loss at a higher rate than all groups (p<0.001). At the end of the study, negative effects of cisplatin on both cellular dimensions (cytoplasmic vacuolization, cell degeneration, dilatation, apoptotic cells, nerve degeneration) and hearing function were observed. No protective or therapeutic effect of PRP on cisplatin ototoxicity was observed.
CONCLUSION
Our study showed that platelet-rich plasma did not have a significant effect in the treatment of hearing loss due to cisplatin ototoxicity and in preventing hearing loss in rats.
PubMed: 37727820
DOI: 10.4274/tao.2023.2022-7-9 -
The South African Journal of... Jan 2022National information regarding ototoxicity monitoring practices are limited for patients undergoing chemotherapy in South Africa.
BACKGROUND
National information regarding ototoxicity monitoring practices are limited for patients undergoing chemotherapy in South Africa.
OBJECTIVES
To determine (1) the national status of ototoxicity monitoring implemented in private and public cancer facilities, (2) the knowledge and ototoxicity monitoring approaches implemented, and (3) reported challenges.
METHOD
A descriptive quantitative survey was conducted in public and private oncology units and audiology referral clinics. Private (60%) and public (43%) oncology units that provide platinum-based chemotherapy in South Africa and audiology referral units (54%) were: (1) surveyed telephonically to determine if ototoxicity monitoring takes place; and (2) a self-administered survey was sent to qualifying oncology units and audiology referral clinics.
RESULTS
All public oncology units reported that ototoxicity monitoring only occurs on referral and is not standard practice. All private oncology units indicated that monitoring is on a patient self-referral basis when symptoms occur. Poor awareness of ototoxicity monitoring best practice guidelines was reported by all oncology units and 14% of audiology referral clinics. Audiology referral clinics reported adequate knowledge of ototoxicity protocols although they are not widely used with only 43% following best practice guidelines. The most prominent challenges reported by participants was referral system (67% oncology units; 57% audiology referral clinics), environmental noise (83% oncology units; 86% audiology referral clinics) and the compromised status of cancer patients (67% oncology units; 57% audiology referral clinics).
CONCLUSION
Ototoxicity monitoring is not routinely implemented across oncology units in South Africa. Multidisciplinary teamwork and a simplified national ototoxicity monitoring protocol may improve hearing outcomes for patients.
Topics: Audiology; Hearing; Hearing Tests; Humans; Neoplasms; Ototoxicity; South Africa
PubMed: 35144440
DOI: 10.4102/sajcd.v69i1.846 -
Frontiers in Cellular Neuroscience 2019Systemic delivery of therapeutics for targeting the cochlea to prevent or treat hearing loss is challenging. Systemic drugs have to cross the blood-labyrinth barrier... (Review)
Review
Systemic delivery of therapeutics for targeting the cochlea to prevent or treat hearing loss is challenging. Systemic drugs have to cross the blood-labyrinth barrier (BLB). BLB can significantly prevent effective penetration of drugs in appropriate concentrations to protect against hearing loss caused by inflammation, ototoxic drugs, or acoustic trauma. This obstacle may be obviated by local administration of protective agents. This route can deliver higher concentration of drug compared to systemic application and preclude systemic side effects. Protective agents have been administered by intra-tympanic injection in numerous preclinical studies. Drugs such as steroids, etanercept, D and L-methionine, pifithrin-alpha, adenosine agonists, melatonin, kenpaullone (a cyclin-dependent kinase 2 (CDK2) inhibitor) have been reported to show efficacy against cisplatin ototoxicity in animal models. Several siRNAs have been shown to ameliorate cisplatin ototoxicity when administered by intra-tympanic injection. The application of corticosteroids and a number of other drugs with adjuvants appears to enhance efficacy. Administration of siRNAs to knock down AMPK kinase, liver kinase B1 (LKB1) or G9a in the cochlea have been found to ameliorate noise-induced hearing loss. The local administration of these compounds appears to be effective in protecting the cochlea against damage from cisplatin or noise trauma. Furthermore the intra-tympanic route yields maximum protection in the basal turn of the cochlea which is most vulnerable to cisplatin ototoxicity and noise trauma. There appears to be very little transfer of these agents to the systemic circulation. This would avoid potential side effects including interference with anti-tumor efficacy of cisplatin. Nanotechnology offers strategies to effectively deliver protective agents to the cochlea. This review summarizes the pharmacology of local drug delivery by intra-tympanic injection to prevent hearing loss caused by cisplatin and noise exposure in animals. Future refinements in local protective agents provide exciting prospects for amelioration of hearing loss resulting from cisplatin or noise exposure.
PubMed: 31338024
DOI: 10.3389/fncel.2019.00300 -
Frontiers in Public Health 2020At this time of the COVID-19 pandemic, potentially effective treatments are currently under urgent investigation. Benefits of chloroquine and hydroxychloroquine for the... (Review)
Review
At this time of the COVID-19 pandemic, potentially effective treatments are currently under urgent investigation. Benefits of chloroquine and hydroxychloroquine for the treatment of COVID-19 infection have been proposed and clinical trials are underway. Chloroquine and hydroxychloroquine, typically used for the treatment of malaria and autoimmune diseases, have been considered for off-label use in several countries. In the literature, there are reports of ototoxic effects of the drugs causing damage to the inner ear structures, which then result in hearing loss, tinnitus, and/or imbalance. This mini-review represents a summary of the findings from a systematic search regarding ototoxicity of chloroquine and hydroxychloroquine in the published literature. The characteristics of sensorineural hearing loss and/or tinnitus after chloroquine or hydroxychloroquine treatment can be temporary but reports of persistent auditory and vestibular dysfunction exist. These are not frequent, but the impact can be substantial. Additionally, abnormal cochleovestibular development in the newborn was also reported after chloroquine treatment in pregnant women. The suggested dose of chloroquine for COVID-19 infection is considerably higher than the usual dosage for malaria treatment; therefore, it is plausible that the ototoxic effects will be greater. There are potential implications from this review for survivors of COVID-19 treated with chloroquine or hydroxychloroquine. Patient reports of hearing loss, tinnitus, or imbalance should be noted. Those with troublesome hearing loss, tinnitus and/or imbalance are encouraged to be referred for hearing evaluation and interventions once they are stable. Clinical trials of chloroquine or hydroxychloroquine should also consider including audiological monitoring in the protocol.
Topics: Antimalarials; Antiviral Agents; Chloroquine; Emergencies; Hearing Loss; Humans; Hydroxychloroquine; Ototoxicity; Public Health; SARS-CoV-2; Tinnitus; COVID-19 Drug Treatment
PubMed: 32574312
DOI: 10.3389/fpubh.2020.00252 -
The Lancet. Oncology Jan 2019Childhood, adolescent, and young adult (CAYA) cancer survivors treated with platinum-based drugs, head or brain radiotherapy, or both have an increased risk of... (Review)
Review
Recommendations for ototoxicity surveillance for childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCare Consortium.
Childhood, adolescent, and young adult (CAYA) cancer survivors treated with platinum-based drugs, head or brain radiotherapy, or both have an increased risk of ototoxicity (hearing loss, tinnitus, or both). To ensure optimal care and reduce consequent problems-such as speech and language, social-emotional development, and learning difficulties-for these CAYA cancer survivors, clinical practice guidelines for monitoring ototoxicity are essential. The implementation of surveillance across clinical settings is hindered by differences in definitions of hearing loss, recommendations for surveillance modalities, and remediation. To address these deficiencies, the International Guideline Harmonization Group organised an international multidisciplinary panel, including 32 experts from ten countries, to evaluate the quality of evidence for ototoxicity following platinum-based chemotherapy and head or brain radiotherapy, and formulate and harmonise ototoxicity surveillance recommendations for CAYA cancer survivors.
Topics: Adolescent; Antineoplastic Agents; Cancer Survivors; Child; Cranial Irradiation; Delivery of Health Care; Evidence-Based Medicine; Humans; Neoplasms; Ototoxicity; Platinum Compounds; Population Surveillance; Young Adult
PubMed: 30614474
DOI: 10.1016/S1470-2045(18)30858-1 -
Anales de Pediatria Nov 2021Ototoxicity occurs in different percentages in patients after treatment with platinum-based chemotherapy or cranial radiation therapy. The aim of this study was to...
INTRODUCTION
Ototoxicity occurs in different percentages in patients after treatment with platinum-based chemotherapy or cranial radiation therapy. The aim of this study was to present our experience in ototoxicity monitoring.
MATERIAL AND METHODS
A review was made of the registry of paediatric cancer patients referred to the Children's Hearing Loss Unit from 1999 to 2019.
RESULTS
Of the 46 patients referred to this unit, 41 had received platinum as part of their treatment, 17 patients underwent neurosurgery, and 18 patients received cranial radiation therapy. An anamnesis and otoscopy were performed on all of them, and the monitoring was carried out with tone-verbal audiometry and/or distortion products. Hearing loss was observed in eight patients (21.05% of patients referred for audiological follow-up) as a consequence of the treatment. It was impossible to determine the audiological situation in eight patients at the end of treatment. Hearing aid adaption was necessary in two patients. In coordination with Paediatric Oncology, a change from cisplatin to carboplatin due to bilateral grade two ototoxicity was considered appropriate during treatment in one patient.
CONCLUSION
Adequate coordination with Paediatric Oncology is essential to carry out active surveillance for ototoxicity and to modify, if possible, the dosage or type of chemotherapy in case hearing is affected. In our experience, and following current recommendations, a pre-treatment assessment is usually performed, as well as monitoring during treatment, at the end of treatment, and annually thereafter due to the risk of a later development of hearing loss.
Topics: Antineoplastic Agents; Cancer Survivors; Carboplatin; Child; Cisplatin; Humans; Neoplasms; Ototoxicity
PubMed: 34702687
DOI: 10.1016/j.anpede.2020.08.014 -
International Journal of... 2021To describe the audio-vestibular disorders related to the newly SARS-CoV-2 infection, including the possible ototoxicity side-effects related to the use of drugs...
To describe the audio-vestibular disorders related to the newly SARS-CoV-2 infection, including the possible ototoxicity side-effects related to the use of drugs included in the SARS-CoV-2 treatment protocols. A systematic review was performed according to the PRISMA protocol. The Medline and Embase databases were searched from March 1, 2020 to April 9, 2021. Initially the search yielded 400 manuscripts, which were reduced to 15, upon the application of inclusion criteria. Sensorineural hearing loss (SNHL) is the most frequent audio-vestibular symptom described, occurring alone or in association with tinnitus and vertigo. The etiopathogenesis of the inner ear disorders related to COVID-19 infection is still poorly understood. The number of reports of COVID-19 infections associated to audio-vestibular disorders is increasing; even if the quality of the studies available is often insufficient, audio-vestibular disorders should be considered as possible manifestations to be included among the symptoms of this infection.
Topics: COVID-19; Hearing Loss, Sensorineural; Humans; Ototoxicity; SARS-CoV-2; Vestibular Diseases
PubMed: 34142589
DOI: 10.1177/20587384211027373