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South African Family Practice :... Mar 2021Ototoxicity is damage to cells in the inner ear after administering a toxic drug, with a resultant hearing loss. Drugs used to treat illnesses such as cancer,... (Review)
Review
BACKGROUND
Ototoxicity is damage to cells in the inner ear after administering a toxic drug, with a resultant hearing loss. Drugs used to treat illnesses such as cancer, tuberculosis, human immuno-deficiency virus (HIV) and infections are potentially ototoxic. South Africa has one of the highest rates of HIV and tuberculosis, and thus a potentially greater degree of the population is being affected by hearing loss from the medications used to treat these illnesses.
METHODS
To determine the current status of research in ototoxicity, a systematic literature review was carried out to determine the focus areas of South African studies for the period 1989-2019. From the database search engines used (Science Direct, Ebscohost and Proquest), a total of 33 relevant articles were identified, including the themes of pharmacology, audiology and knowledge.
RESULTS
Studies were conducted in the three most resourced provinces in South Africa. Findings indicate that there is a need for educating doctors regarding ototoxicity and a delineation of the role of the audiologist in monitoring and management of ototoxic hearing loss. There is a resultant need for audiology training on the pharmacology of ototoxic medication, otoprotective strategies and adherence to recommended guidelines. This has implications for university audiology training programmes and curriculum planning. The need for development of South Africa-specific audiology guidelines was highlighted.
CONCLUSION
Whilst it is noted that there is a lack of resources for effective implementation of ototoxicity-monitoring protocols, it is also noted that there are measures and otoprotective strategies that can be put in place without additional resources.
Topics: Audiologists; Audiology; Ear, Inner; Hearing Loss; Humans; Ototoxicity
PubMed: 33764142
DOI: 10.4102/safp.v63i1.5187 -
Frontiers in Neuroscience 2021Cisplatin-induced ototoxicity in humans is more predominant in the cochlea than in the vestibule. Neither definite nor substantial vestibular dysfunction after cisplatin... (Review)
Review
Cisplatin-induced ototoxicity in humans is more predominant in the cochlea than in the vestibule. Neither definite nor substantial vestibular dysfunction after cisplatin treatment has been consistently reported in the current literature. Inner ear hair cells seem to have intrinsic characteristics that make them susceptible to direct exposure to cisplatin. The existing literature suggests, however, that cisplatin might have different patterns of drug trafficking across the blood-labyrinth-barrier, or different degrees of cisplatin uptake to the hair cells in the cochlear and vestibular compartments. This review proposes an explanation for the preferential cochleotoxicity of cisplatin based on current evidence as well as the anatomy and physiology of the inner ear. The endocochlear potential, generated by the stria vascularis, acting as the driving force for hair cell mechanoelectrical transduction might also augment cisplatin entry into cochlear hair cells. Better understanding of the stria vascularis might shed new light on cochleotoxic mechanisms and inform the development of otoprotective interventions to moderate cisplatin associated ototoxicity.
PubMed: 34381329
DOI: 10.3389/fnins.2021.695268 -
Frontiers in Pharmacology 2020Cisplatin is widely used for the treatment of a number of solid malignant tumors. However, ototoxicity induced by cisplatin is an obstacle to effective treatment of... (Review)
Review
Cisplatin is widely used for the treatment of a number of solid malignant tumors. However, ototoxicity induced by cisplatin is an obstacle to effective treatment of tumors. The basis for this toxicity has not been fully elucidated. It is generally accepted that hearing loss is due to excessive production of reactive oxygen species by cells of the cochlea. In addition, recent data suggest that inflammation may trigger inner ear cell death through endoplasmic reticulum stress, autophagy, and necroptosis, which induce apoptosis. Strategies have been extensively explored by which to prevent, alleviate, and treat cisplatin-induced ototoxicity, which minimize interference with antitumor activity. Of these strategies, none have been approved by the Federal Drug Administration, although several preclinical studies have been promising. This review highlights recent strategies that reduce cisplatin-induced ototoxicity. The focus of this review is to identify candidate agents as novel molecular targets, drug administration routes, delivery systems, and dosage schedules. Animal models of cisplatin ototoxicity are described that have been used to evaluate drug efficacy and side effect prevention. Finally, clinical reports of otoprotection in patients treated with cisplatin are highlighted. For the future, high-quality studies are required to provide reliable data regarding the safety and effectiveness of pharmacological interventions that reduce cisplatin-induced ototoxicity.
PubMed: 32719605
DOI: 10.3389/fphar.2020.00999 -
Antioxidants & Redox Signaling Jun 2022Transient receptor potential (TRP) channels are cation-gated channels that serve as detectors of various sensory modalities, such as pain, heat, cold, and taste. These... (Review)
Review
Transient receptor potential (TRP) channels are cation-gated channels that serve as detectors of various sensory modalities, such as pain, heat, cold, and taste. These channels are expressed in the inner ear, suggesting that they could also contribute to the perception of sound. This review provides more details on the different types of TRP channels that have been identified in the cochlea to date, focusing on their cochlear distribution, regulation, and potential contributions to auditory functions. To date, the effect of TRP channels on normal cochlear physiology in mammals is still unclear. These channels contribute, to a limited extent, to normal cochlear physiology such as the hair cell mechanoelectrical transduction channel and strial functions. More detailed information on a number of these channels in the cochlea awaits future studies. Several laboratories focusing on TRPV1 channels have shown that they are responsive to cochlear stressors, such as ototoxic drugs and noise, and regulate cytoprotective and/or cell death pathways. TRPV1 expression in the cochlea is under control of oxidative stress (produced primarily by NOX3 NADPH oxidase) as well as STAT1 and STAT3 transcription factors, which differentially modulate inflammatory and apoptotic signals in the cochlea. Inhibition of oxidative stress or inflammation reduces the expression of TRPV1 channels and protects against cochlear damage and hearing loss. TRPV1 channels are activated by both capsaicin and cisplatin, which produce differential effects on the inner ear. How these differential actions are produced is yet to be determined. It is clear that TRPV1 is an essential component of cisplatin ototoxicity as knockdown of these channels protects against hearing loss. In contrast, activation of TRPV1 by capsaicin protected against subsequent hearing loss induced by cisplatin. The cellular targets that are influenced by these two drugs to account for their differential profiles need to be fully elucidated. Furthermore, the potential involvement of different TRP channels present in the cochlea in regulating cisplatin ototoxicity needs to be determined. TRPV1 has been shown to mediate the entry of aminoglycosides into the hair cells. Thus, novel otoprotective strategies could involve designing drugs to inhibit entry of aminoglycosides and possibly other ototoxins into cochlear hair cells. TRP channels, including TRPV1, are expressed on circulating and resident immune cells. These receptors modulate immune cell functions. However, whether they are activated by cochlear stressors to initiate cochlear inflammation and ototoxicity needs to be determined. A better understanding of the function and regulation of these TRP channels in the cochlea could enable development of novel treatments for treating hearing loss. . 36, 1158-1170.
Topics: Aminoglycosides; Animals; Capsaicin; Cisplatin; Hearing Loss; Inflammation; Mammals; Ototoxicity; Transient Receptor Potential Channels
PubMed: 34465184
DOI: 10.1089/ars.2021.0191 -
Frontiers in Cellular Neuroscience 2021Aminoglycosides, a class of clinically important drugs, are widely used worldwide against gram-negative bacterial infections. However, there is growing evidence that... (Review)
Review
Aminoglycosides, a class of clinically important drugs, are widely used worldwide against gram-negative bacterial infections. However, there is growing evidence that aminoglycosides can cause hearing loss or balance problems. In this article, we mainly introduce the main mechanism of ototoxicity induced by aminoglycosides. Genetic analysis showed that the susceptibility of aminoglycosides was attributable to mutations in mtDNA, especially A1555G and C1494T mutations in 12S rRNA. In addition, the overexpression of NMDA receptors and the formation of free radicals also play an important role. Understanding the mechanism of ototoxicity induced by aminoglycosides is helpful to develop new therapeutic methods to protect hearing. In this article, the prevention methods of ototoxicity induced by aminoglycosides were introduced from the upstream and downstream aspects.
PubMed: 34211374
DOI: 10.3389/fncel.2021.692762 -
Frontiers in Pharmacology 2021Hearing loss is a major unresolved problem in the world, which has brought a heavy burden to society, economy, and families. Hair cell damage and loss mediated by... (Review)
Review
Hearing loss is a major unresolved problem in the world, which has brought a heavy burden to society, economy, and families. Hair cell damage and loss mediated by oxidative stress are considered to be important causes of hearing loss. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator of antioxidant capacity and is involved in the occurrence and development of a series of toxic and chronic diseases associated with oxidative stress. In recent years, studies on the correlation between hearing loss and Nrf2 target have continuously broadened our knowledge, and Nrf2 has become a new strategic target for the development and reuse of hearing protection drugs. This review summarized the correlation of Nrf2 in various types of hearing loss, and the role of drugs in hearing protection through Nrf2 from the literature.
PubMed: 33912042
DOI: 10.3389/fphar.2021.620921 -
BioRxiv : the Preprint Server For... Nov 2023Cisplatin is a widely used and highly effective anti-cancer drug with significant side effects including ototoxicity and nephrotoxicity. Macrophages, the major resident...
Cisplatin is a widely used and highly effective anti-cancer drug with significant side effects including ototoxicity and nephrotoxicity. Macrophages, the major resident immune cells in the cochlea and kidney, are important drivers of both inflammatory and tissue repair responses. To investigate the roles of macrophages in cisplatin-induced ototoxicity and nephrotoxicity, we used PLX3397, an FDA-approved inhibitor of the colony-stimulating factor 1 receptor (CSF1R), to eliminate tissue-resident macrophages during the course of cisplatin administration. Mice treated with cisplatin alone (cisplatin/vehicle) had significant hearing loss (ototoxicity) as well as kidney injury (nephrotoxicity). Macrophage ablation using PLX3397 resulted in significantly reduced hearing loss measured by auditory brainstem responses (ABR) and distortion-product otoacoustic emissions (DPOAE). Sensory hair cells in the cochlea were protected against cisplatin-induced death in mice treated with PLX3397. Macrophage ablation also protected against cisplatin-induced nephrotoxicity, as evidenced by markedly reduced tubular injury and fibrosis as well as reduced plasma blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels. Mechanistically, our data suggest that the protective effect of macrophage ablation against cisplatin-induced ototoxicity and nephrotoxicity is mediated by reduced platinum accumulation in both the inner ear and the kidney. Together our data indicate that ablation of tissue-resident macrophages represents a novel strategy for mitigating cisplatin-induced ototoxicity and nephrotoxicity.
PubMed: 38014097
DOI: 10.1101/2023.11.16.567274 -
JAC-antimicrobial Resistance Dec 2021Ototoxicity has been reported after administration of aminoglycosides and glycopeptides. (Review)
Review
BACKGROUND
Ototoxicity has been reported after administration of aminoglycosides and glycopeptides.
OBJECTIVES
To identify available evidence for the occurrence and determinants of aminoglycoside- and glycopeptide-related ototoxicity in children.
MATERIALS AND METHODS
Systematic electronic literature searches that combined ototoxicity (hearing loss, tinnitus and/or vertigo) with intravenous aminoglycoside and/or glycopeptide administration in children were performed in PubMed, EMBASE and Cochrane Library databases. Studies with sample sizes of ≥50 children were included. The QUIPS tool and Cochrane criteria were used to assess the quality and risk of bias of included studies.
RESULTS
Twenty-nine aminoglycoside-ototoxicity studies met the selection criteria (including 7 randomized controlled trials). Overall study quality was medium/low. The frequency of hearing loss within these studies ranged from 0%-57%, whereas the frequency of tinnitus and vertigo ranged between 0%-53% and 0%-79%, respectively. Two studies met the criteria on glycopeptide-induced ototoxicity and reported hearing loss frequencies of 54% and 55%. Hearing loss frequencies were higher in gentamicin-treated children compared to those treated with other aminoglycosides. In available studies aminoglycosides had most often been administered concomitantly with platinum agents, diuretics and other co-medication.
CONCLUSIONS
In children the reported occurrence of aminoglycoside/glycopeptide ototoxicity highly varies and seems to depend on the diagnosis, aminoglycoside subtype and use of co-administered medication. More research is needed to investigate the prevalence and determinants of aminoglycoside/glycopeptide ototoxicity. Our results indicate that age-dependent audiological examination may be considered for children frequently treated with aminoglycosides/glycopeptides especially if combined with other ototoxic medication.
PubMed: 34917943
DOI: 10.1093/jacamr/dlab184 -
The South African Journal of... May 2020Treatment of cancer with cisplatin can result in hearing loss. Given the increasing burden of cancer in Africa, appropriate and timely identification, intervention and...
BACKGROUND
Treatment of cancer with cisplatin can result in hearing loss. Given the increasing burden of cancer in Africa, appropriate and timely identification, intervention and management of hearing loss in affected patients is of paramount importance.
OBJECTIVES
This study describes the perspectives and practices of healthcare professionals in relation to cisplatin-associated ototoxicity at an institution treating patients diagnosed with cancer.
METHOD
A concurrent triangulation study design was used to collect quantitative data from seven oncologists, nine nurses and 13 pharmacists using self-administered questionnaires, and qualitative data from four audiologists through semi-structured interviews for this hospital-based study, conducted in South Africa.
RESULTS
Levels of awareness of cisplatin-associated ototoxicity varied with only 33% of the nursing personnel being aware in comparison to the oncologists and pharmacists. Oncologists were identified as the main custodians for providing information to patients. Whilst 82% of the participants considered the audiologist to be part of the oncology team, there was no provision for ototoxicity monitoring in the chemotherapy protocols, nor any ototoxicity-monitoring programme in place. There was no evidence that knowledge of cisplatin-associated ototoxicity translated into an appropriate management strategy for such patients.
CONCLUSION
Healthcare personnel overseeing the care and management of cancer patients need to improve their awareness of ototoxicity and refer timeously for audiological evaluation. Audiologists require greater awareness of monitoring programmes to appropriately implement and manage such programmes within a cancer platform and be part of a multidisciplinary team.
Topics: Antineoplastic Agents; Cisplatin; Female; Health Knowledge, Attitudes, Practice; Hearing Loss; Humans; Male; Medical Oncology; Neoplasms; Ototoxicity; Qualitative Research; South Africa; Surveys and Questionnaires
PubMed: 32501032
DOI: 10.4102/sajcd.v67i1.685