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Frontiers in Neurology 2020
PubMed: 33193062
DOI: 10.3389/fneur.2020.593917 -
BioMed Research International 2021Cisplatin is an efficacious anticancer agent, but its use is limited by ototoxicity and resultant irreversible sensorineural hearing loss. Cisplatin ototoxicity is...
Cisplatin is an efficacious anticancer agent, but its use is limited by ototoxicity and resultant irreversible sensorineural hearing loss. Cisplatin ototoxicity is associated with cochlear cell oxidative stress and mitochondrial damage. However, mitophagy is vital for maintaining mitochondrial quality and cellular metabolism. Accordingly, we investigated the role of mitophagy in regulating cisplatin-induced ototoxicity using the auditory cell line HEI-OC1. In this study, HEI-OC1 cells were treated with either cisplatin alone (10 M, 0, 8, 16, and 24 h); cisplatin (10 M, 24 h) post transfection with small-interfering (si)RNAs targeting mitophagy-associated mRNAs; cisplatin (10 M, 24 h) succeeding pretreatment with the mitophagy suppressor, 3-methyladenine (3-MA; 5 or 10 mM, 6 h); or cisplatin (30 M, 24 h) following pretreatment with the mitophagy promoter, carbonyl cyanide m-chlorophenylhydrazone (CCCP; 1 or 2 M, 2 h). The viability of cells, expression of mitophagy marker, and mitochondrial functions were then assessed in these cells. Cell viability was determined by a water-soluble tetrazolium assay; expression of mitophagy-associated proteins , , , , p62, and LC3B was analyzed by Western blotting, mitochondrial membrane potential by flow cytometry, intracellular ATP by spectrophotometry, and mitochondrial degradation by dual staining for mitochondria and autophagosomes or lysosomes. Our results showed that cisplatin gradually reduced the viable cell number over time, induced mitochondrial depolarization, decreased intracellular ATP concentration, and enhanced the expression of , , , p62, and LC3B. In addition, and knockdown accelerated cisplatin-induced loss of cell viability, mitochondrial membrane potential, mitophagosome/lysosome formation, and reduction in intracellular ATP production. Pretreatment with 3-MA aggravated the cisplatin-induced cytotoxicity, while that with CCCP reversed this effect. Overall, our findings indicate that mitophagy protects HEI-OC1 cells against cisplatin-induced cell death. Consequently, we strongly believe that targeted promotion of mitophagy may confer protection against cisplatin-induced ototoxicity.
Topics: Apoptosis; Autophagosomes; Cell Line, Tumor; Cell Survival; Cisplatin; Hearing Loss, Sensorineural; Humans; Membrane Potential, Mitochondrial; Membrane Proteins; Mitochondria; Mitophagy; Ototoxicity; Proto-Oncogene Proteins; RNA, Small Interfering; Reactive Oxygen Species; Ubiquitin-Protein Ligases
PubMed: 34095303
DOI: 10.1155/2021/5590973 -
American Journal of Otolaryngology 2021Current clinical evidences do not support any specific treatment against SARS-CoV-2. Chloroquine (CQ) and hydroxychloroquine (HCQ) are typically used in the treatment of... (Review)
Review
INTRODUCTION
Current clinical evidences do not support any specific treatment against SARS-CoV-2. Chloroquine (CQ) and hydroxychloroquine (HCQ) are typically used in the treatment of rheumatoid arthritis, systemic lupus erythematosus and malaria; they have been considered for off-label and compassionate use in several countries against moderate to severe cases of COVID-19 and there's actually a massive demand of these two drugs. The aim of this paper is to briefly review the published literature, summarizing evidences about audiological implications after CQ and HCQ treatment.
METHODS
We conducted a review of the literature on Medline and Pubmed platforms from 27th May 2020 to 30 May 2020. We combined MeSH terms of "chloroquine", "hydroxychloroquine", "ototoxicity", "hearing loss", "tinnitus", "deafness" and "hearing". Publications with relevant data were included. Selected data (authors, country and year; sample size; study design; audiological side effects) were extracted and summarized in a table.
RESULTS
Of 45 initial studies, 14 met inclusion criteria. The authors found xix cases of HCQ ototoxicity; Tinnitus was reported in 2 cases, and it was found to be reversible or irreversible. Sensorineural hearing loss after HCQ use was reported in 7 patients; it was found to be irreversible or partially reversible after discontinuation of HCQ in 6 cases. Eight papers reporting CQ ototoxicity were; tinnitus was not reported by any authors. Sensorineural hearing loss after taking CQ was reported in 6 patients; it was found to be irreversible after discontinuation of CQ in 5 patients. One patient showed abnormal gait after a single intramuscular injection of CQ. Thirteen patients' Auditory Brainstem Response (ABR) were found to be abnormal, but they resolved after CQ discontinuation.
CONCLUSIONS
CQ and HCQ related ototoxicity is widely reported in the literature although the pathophysiological mechanism is not well known. Current data are not sufficient enough to support the use of CQ and HCQ as therapy for COVID-19, but considering the growing demand for these two drugs and the number of people around the world who have taken and will take CQ and HCQ, it must necessarily consider the clinical and social impact of long term audiological side effects.
Topics: Antirheumatic Agents; Humans; Hydroxychloroquine; Ototoxicity; COVID-19 Drug Treatment
PubMed: 33780902
DOI: 10.1016/j.amjoto.2020.102640 -
Archives of Toxicology Aug 2021Vestibular hair cells are mechanosensory receptors that are capable of detecting changes in head position and thereby allow animals to maintain their posture and... (Review)
Review
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.
Topics: Aging; Animals; Epithelium; Hair Cells, Vestibular; Humans; Ototoxicity; Vestibular Diseases
PubMed: 33983457
DOI: 10.1007/s00204-021-03067-3 -
The International Journal of... Sep 2019Treatment of multidrug-resistant tuberculosis (MDR-TB) is lengthy and utilizes second-line anti-TB drugs associated with frequent adverse drug reactions (ADRs). To...
Treatment of multidrug-resistant tuberculosis (MDR-TB) is lengthy and utilizes second-line anti-TB drugs associated with frequent adverse drug reactions (ADRs). To evaluate the prevalence of and risk factors for ADRs among patients with MDR- and extensively drug-resistant TB (XDR-TB). A retrospective chart review of patients initiating treatment for M/XDR-TB in 2010-2012 in Tbilisi, Georgia. Eighty (54%) and 38 (26%) of 147 patients developed nephrotoxicity per RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification and ototoxicity, respectively. Twenty-five (17%) patients required permanent interruption of injectables due to an ADR. Median hospital stay, total treatment duration and number of regimen changes were higher among those with nephrotoxicity and/or ototoxicity, compared to those without ( < 0.01). Multinomial logistic regression analysis identified increasing age (per year) as a risk factor for nephrotoxicity (aOR 1.08, 95%CI 1.03-1.12) and for both, nephro- and ototoxicity (aOR 1.11, 95%CI 1.05-1.17). Low baseline creatinine clearance (CrCl) was a significant risk factor for developing nephrotoxicity (aOR 1.05, 95%CI 1.02-1.07). Second-line injectable drug-related ADRs are common among M/XDR-TB patients. Patients with increasing age and low baseline CrCl should be monitored closely for injectable-related ADRs. Notably, our findings support WHO's latest recommendations on introduction of injectable free anti-TB treatment regimens.
Topics: Adolescent; Adult; Aged; Antitubercular Agents; Extensively Drug-Resistant Tuberculosis; Female; Georgia (Republic); Humans; Kidney Diseases; Male; Middle Aged; Ototoxicity; Prevalence; Retrospective Studies; Risk Factors; Tuberculosis, Multidrug-Resistant; Young Adult
PubMed: 31615608
DOI: 10.5588/ijtld.18.0626 -
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 -
Kidney International Oct 2007This paper reviews intriguing recent findings on the mechanisms of drug induced hearing loss caused by two major classes of therapeutic agents: the aminoglycoside... (Review)
Review
This paper reviews intriguing recent findings on the mechanisms of drug induced hearing loss caused by two major classes of therapeutic agents: the aminoglycoside antibiotics and cisplatin. Both drug categories are nephrotoxic as well as ototoxic. Aminoglycosides and cisplatin target the outer hair cells in the basal turn of the cochlea to cause high frequency sensorineural hearing loss in a substantial percentage of patients treated with these drugs. Each group of agents appears to generate reactive oxygen species within the cochlea that trigger downstream mechanisms leading to cell death. Various protective agents including antioxidants show promise in protecting the inner ear from damage in experimental animals. The only successful double-blind, placebo controlled clinical trial using a protective agent to prevent ototoxicity was carried out in China. Aspirin or placebo was given in combination with gentamicin. A significant decrease in hearing loss was observed. Successful clinical implementation of protective agents will require a cautious approach, so that the therapeutic effect of the anti-infective agent or anti-neoplastic drug is not attenuated. This may require novel methods of administration of protective agents, such as injection within the middle ear. This would provide a maximal dose of protective agent without systemic interference with the desired effect of the ototoxic agent.
Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Antineoplastic Agents; Antioxidants; Cisplatin; Hearing Loss; Humans; Kidney Diseases
PubMed: 17653135
DOI: 10.1038/sj.ki.5002434 -
East African Medical Journal Oct 2005Systemic ototoxicity is a significant cause of vestibulocochlear morbidity in sub-Saharan Africa. It may result in permanent hearing impairment and/or balance problems. (Review)
Review
BACKGROUND
Systemic ototoxicity is a significant cause of vestibulocochlear morbidity in sub-Saharan Africa. It may result in permanent hearing impairment and/or balance problems.
OBJECTIVES
To review the literature pertaining to the ototoxic potential of three frequently prescribed systemic medications in the sub-Saharan setting; quinine, furosemide and aminoglycoside antibiotics. The pathophysiology, clinical manifestations and risk factors and risk minimisation strategies regarding the ototoxicity associated with these drugs are presented in order to highlight this problem and reduce the incidence of adverse outcomes.
DATA SOURCES
The biomedical literature was systematically reviewed. This included a search of the National Library of Medicine's PubMed database (http://www.ncbi.nlm.nih.gov/ entrez/query.fcgi?db=PubMed). The search was limited to the English language literature and used the following search terms: ototoxicity; aminoglycosides; quinine; furosemide; gentamicin; vestibular toxicity; auditory toxicity; and Africa.
STUDY SELECTION
Studies and reviews directly addressing clinical ototoxicity, experimental studies and studies regarding ototoxicity in sub-Saharan Africa were reviewed. The authors formed a consensus opinion regarding the most relevant articles considering factors including evidence level.
DATA EXTRACTION
Systematic data extraction was undertaken from relevant studies.
CONCLUSIONS
Quinine, furosemide and aminoglycosides are potentially ototoxic. High doses, prolonged treatment and intravenous administration increase this risk. The clinical condition of the patient may further predispose patients to ototoxic damage. Lack of monitoring facilities and efficacious, cost effective alternatives increase the risks of ototoxicity in the African setting. Clinicians must be aware of these risks and those patients at increased risk, and be vigilant in recognising their clinical manifestations.
Topics: Africa South of the Sahara; Aminoglycosides; Antimalarials; Diuretics; Drug-Related Side Effects and Adverse Reactions; Furosemide; Hearing Loss; Humans; Quinine; Risk Assessment; Risk Factors; Vestibulocochlear Nerve Diseases
PubMed: 16450683
DOI: 10.4314/eamj.v82i10.9353 -
Cancer Chemotherapy and Pharmacology Feb 2020Ototoxicity associated with platinum-based chemotherapy is highly prevalent and can cause detrimental consequences among cancer survivors. (Review)
Review
INTRODUCTION
Ototoxicity associated with platinum-based chemotherapy is highly prevalent and can cause detrimental consequences among cancer survivors.
DISCUSSION
In this article, we highlight important aspects of the evaluation of ototoxicity with the aim to increase awareness of Oncologists in this regard. Standard pure tone audiometry alone is inadequate for this context. Comprehensive and consistent hearing tests should be implemented in a monitoring and surveillance program. High-frequency audiometry (10-16 kHz) is a sensitive tool in the detection of ototoxic hearing loss at onset. In addition to threshold audiometry, measures of speech comprehension (both in quiet and in noise) can add useful information in the evaluation of hearing in real-life situations. Not only hearing loss, but also tinnitus and imbalance are common in patients who receive platinum-based chemotherapy, and can cause debilitating effects upon quality of life in this population. Moreover, self-report measures associated with cochlear and vestibular handicaps can provide valuable information regarding the impact of ototoxicity.
CONCLUSIONS
It is vital to build awareness about the variety and impact of the symptoms of ototoxicity. Comprehensive evaluation of hearing status along with self-reported impact of the cochlear and vestibular handicap should be implemented in a monitoring and surveillance program for appropriate investigation and management.
Topics: Antineoplastic Agents; Hearing; Hearing Loss; Humans; Organoplatinum Compounds; Ototoxicity
PubMed: 31865419
DOI: 10.1007/s00280-019-04012-z -
Revista Da Associacao Medica Brasileira... 2021To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine...
OBJECTIVE
To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine (HCQ).
METHODS
The studies were selected using a combination based on the Medical Subject Headings (MeSH). The databases searched were MEDLINE (PubMed), LILACS, SciELO, and BIREME, encompassing articles from January 2010 to May 2020, with no restrictions of language and place of publication.
RESULTS
A total of 148 articles with the potential to be included were retrieved. Of these, two answered the research question, which consisted of seeking evidence of the ototoxic effects of hydroxychloroquine. These studies scored 11 in their quality assessment with the modified protocol by Pithon et al.13.
CONCLUSIONS
The studies reported possible ototoxicity of HCQ. Audiovestibular changes, such as hearing loss, peripheral vestibular syndrome, and tinnitus were evidenced in patients submitted to HCQ. The improvement in the audiological examinations and the regression in the vestibular syndrome after stopping the treatment with HCQ are strong arguments in favor of the ototoxicity caused by this medication. However, there are still divergences about the relationship between ototoxic effects and the use of HCQ.
Topics: Hearing Loss; Humans; Hydroxychloroquine; Ototoxicity
PubMed: 34259762
DOI: 10.1590/1806-9282.67.Suppl1.20200677