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CNS Neuroscience & Therapeutics Feb 2024Cinchonine (CN) and its isomer cinchonidine (CD), two of the common cinchona alkaloids, are wildly used as antimalarial drugs. However, the effects of CN and CD on the...
AIM
Cinchonine (CN) and its isomer cinchonidine (CD), two of the common cinchona alkaloids, are wildly used as antimalarial drugs. However, the effects of CN and CD on the auditory system are unknown.
METHODS
Molecular docking and molecular dynamics (MD) simulation were used for predicting effective drugs. The CCK-8 assay was conducted for assessing cell viability in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. MitoSox Red staining revealed reactive oxygen species (ROS) amounts. TMRM staining was used to assess the mitochondrial membrane potential (ΔΨm). Immunofluorescence staining of myosin 7a was used to examine hair cells (HCs) in cisplatin-treated neonatal mouse cochlear explants, while TUJ-1 immunostaining was used for the detection of spiral ganglion neurons (SGNs). Cleaved caspase-3 and TUNEL immunostaining were utilized for apoptosis assessment. Immunoblot was carried out to detect PI3K-AKT signaling effectors.
RESULTS
Pretreatment with CN or CD significantly increased cell viability and reduced mitochondrial dysfunction and ROS accumulation in cisplatin-treated HEI-OC1 cells. Immunofluorescent staining of cochlear explants showed that CN and CD attenuated cisplatin-induced damage to SGNs and HCs. Immunoblot revealed that CN and CD downregulated the expression of cleaved caspase-3 and activated PI3K-AKT signaling in cisplatin-injured HEI-OC1 cells.
CONCLUSION
CD and CN can reduce ototoxicity caused by cisplatin and might help treat cisplatin-associated hearing loss.
Topics: Mice; Animals; Cisplatin; Antineoplastic Agents; Proto-Oncogene Proteins c-akt; Caspase 3; Phosphatidylinositol 3-Kinases; Reactive Oxygen Species; Ototoxicity; Molecular Docking Simulation; Cinchona Alkaloids; Apoptosis
PubMed: 37577804
DOI: 10.1111/cns.14403 -
Cadernos de Saude Publica Jul 2012Mercury is neurotoxic, and numerous studies have confirmed its ototoxic effect. However, the diagnosis and follow-up of mercury exposure require understanding the... (Review)
Review
Mercury is neurotoxic, and numerous studies have confirmed its ototoxic effect. However, the diagnosis and follow-up of mercury exposure require understanding the pathophysiology of the chemical substance. Based on a systematic literature review, this study aimed to demonstrate whether mercury is ototoxic and to analyze its mechanism of action on the peripheral and central auditory system, in order to contribute to the diagnosis and follow-up of exposure. This was a systematic review of studies published on the effects of mercury exposure on the auditory system. The full text of the studies and their methodological quality were analyzed. The review identified 108 studies published on the theme, of which 28 met the inclusion criteria. All the articles in the analysis showed that mercury exposure is ototoxic and produces peripheral and/or central damage. Acute and long-term exposure produces irreversible damage to the central auditory system. Biomarkers were unable to predict the relationship between degree of mercury poisoning and degree of lesion in the auditory system.
Topics: Ear Diseases; Environmental Exposure; Hearing Loss; Humans; Mercury; Severity of Illness Index; Time Factors
PubMed: 22729255
DOI: 10.1590/s0102-311x2012000700003 -
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 -
Journal of Toxicology 2016Cisplatin is an effective drug used in the treatment of many cancers, yet its ototoxic potential places cancer patients, exposed to this drug, at risk of hearing loss,... (Review)
Review
Cisplatin is an effective drug used in the treatment of many cancers, yet its ototoxic potential places cancer patients, exposed to this drug, at risk of hearing loss, thus negatively impacting further on a patient's quality of life. It is paramount for health care practitioners managing such patients to be aware of cisplatin's ototoxic properties and the clinical signs to identify patients at risk of developing hearing loss. English peer-reviewed articles from January 1975 to July 2015 were assessed from PubMed, Science Direct, and Ebscohost. Seventy-nine articles and two books were identified for this review, using MeSH terms and keywords such as "ototoxicity", "cisplatin", "hearing loss", and "ototoxicity monitoring". This review provides an up-to-date overview of cisplatin-associated ototoxicity, namely, its clinical features, incidence rates, and molecular and cellular mechanisms and risk factors, to health care practitioners managing the patient with cancer, and highlights the need for a team-based approach to complement an audiological monitoring programme to mitigate any further loss in the quality of life of affected patients, as there is currently no otoprotective agent recommended routinely for the prevention of cisplatin-associated ototoxicity. It also sets the platform for effective dialogue towards policy formulation and strengthening of health systems in developing countries.
PubMed: 28115933
DOI: 10.1155/2016/1809394 -
Medicine Nov 2022Hearing damage is one of the main toxic effects of platinum compounds, it derives from the irreversible degeneration of hair cells of the ear. Genetic association...
Hearing damage is one of the main toxic effects of platinum compounds, it derives from the irreversible degeneration of hair cells of the ear. Genetic association studies have suggested an association between GSTP1 c.313A>G variant and platinum-induced ototoxicity in childhood cancer survivors. We aimed to detect the frequency of ototoxicity and associated risk factors in survivors of childhood cancer receiving platinum-based chemotherapy and to detect the relation between GSTP1 c.313A>G (rs1695) polymorphisms and ototoxicity. We conducted a cross-sectional study on 64 cancer survivors who received platinum agents (cisplatin and/or carboplatin) at least 2 years after the end of chemotherapy. The patients underwent comprehensive audiological evaluations and genotyping to detect the presence of the GSTP1 c.313A>G polymorphisms. Hearing loss (HL) was identified in 16/64 patients (25%), including 62.5% treated with cisplatin and 37.5% treated with carboplatin. The greater incidence of ototoxicity was found in children treated for osteosarcoma (28.1%) followed by patients with germ cell tumors (25%) and neuroblastoma (21.9%). The AA, AG, and GG types of GSTP1 c.313A>G variant were detected in 84.4%, 9.4%, and 6.3%, respectively, of patients with HL with a significant association between mutant genotype of GSTP1 rs1695 and platinum-induced ototoxicity (P = .035). HL was not significantly associated with the total cumulative dose of cisplatin and carboplatin. GSTP1 c.313A>G variant may increase the risk of HL in pediatric oncology patients treated with cisplatin or carboplatin chemotherapy.
Topics: Child; Humans; Cancer Survivors; Carboplatin; Ototoxicity; Cisplatin; Platinum; Cross-Sectional Studies; Neoplasms; Glutathione S-Transferase pi; Hearing Loss; Deafness
PubMed: 36397425
DOI: 10.1097/MD.0000000000031627 -
Frontiers in Immunology 2023Cisplatin is chemotherapy used for solid tumor treatment like lung, bladder, head and neck, ovarian and testicular cancers. However, cisplatin-induced ototoxicity limits...
Cisplatin is chemotherapy used for solid tumor treatment like lung, bladder, head and neck, ovarian and testicular cancers. However, cisplatin-induced ototoxicity limits the utility of this agent in cancer patients, especially when dose escalations are needed. Ototoxicity is associated with cochlear cell death through DNA damage, the generation of reactive oxygen species (ROS) and the consequent activation of caspase, glutamate excitotoxicity, inflammation, apoptosis and/or necrosis. Previous studies have demonstrated a role of CXC chemokines in cisplatin ototoxicity. In this study, we investigated the role of CXCL1, a cytokine which increased in the serum and cochlea by 24 h following cisplatin administration. Adult male Wistar rats treated with cisplatin demonstrated significant hearing loss, assessed by auditory brainstem responses (ABRs), hair cell loss and loss of ribbon synapse. Immunohistochemical studies evaluated the levels of CXCL1 along with increased presence of CD68 and CD45-positive immune cells in cochlea. Increases in CXCL1 was time-dependent in the spiral ganglion neurons and organ of Corti and was associated with progressive increases in CD45, CD68 and IBA1-positive immune cells. Trans-tympanic administration of SB225002, a chemical inhibitor of CXCR2 (receptor target for CXCL1) reduced immune cell migration, protected against cisplatin-induced hearing loss and preserved hair cell integrity. We show that SB225002 reduced the expression of , , , , and . Similarly, knockdown of by trans-tympanic administration of siRNA protected against hearing loss and loss of outer hair cells and reduced ribbon synapses. In addition, SB225002 reduced the expression of inflammatory mediators induced by cisplatin. These results implicate the CXCL1 chemokine as an early player in cisplatin ototoxicity, possibly by initiating the immune cascade, and indicate that CXCR2 is a relevant target for treating cisplatin ototoxicity.
Topics: Rats; Animals; Male; Cisplatin; Chemokine CXCL1; Ototoxicity; Rats, Wistar; NADPH Oxidases; Hearing Loss
PubMed: 37063917
DOI: 10.3389/fimmu.2023.1125948 -
Journal of Cancer Research and... Apr 2023Chemotherapeutic agents can have both serious side effects and ototoxicity, which can be caused by direct toxic effects or by metabolic derangement by the agents....
INTRODUCTION
Chemotherapeutic agents can have both serious side effects and ototoxicity, which can be caused by direct toxic effects or by metabolic derangement by the agents. Cabazitaxel (CBZ) is a next-generation semi-synthetic taxane derivative that is effective in both preclinical models of human tumors that are sensitive or resistant to chemotherapy and in patients suffering from progressive prostate cancer despite docetaxel treatment. The primary aim of this study is to investigate the ototoxicity of CBZ in a rat model.
MATERIALS AND METHODS
: A total of 24 adult male Wistar-Albino rats were equally and randomly divided into four groups. CBZ (Jevtana, Sanofi-Aventis USA) was intraperitoneally administered to Groups 2, 3, and 4 at doses of 0.5, 1.0, and 1.5 mg/kg/week, respectively, for 4 consecutive weeks; Group 1 received only i.p. saline at the same time. At the end of the study, the animals were sacrificed and their cochlea removed for histopathological examination.
RESULTS
: Intraperitoneal administration of CBZ exerted an ototoxic effect on rats, and the histopathological results became worse in a dose-dependent manner (P < 0.05).
CONCLUSION
: Our findings suggest that CBZ may be an ototoxic agent and can damage the cochlea. More clinical studies should be conducted to understand its ototoxicity.
Topics: Humans; Animals; Rats; Male; Antineoplastic Agents; Ototoxicity; Rats, Wistar; Cochlea; Prostatic Neoplasms
PubMed: 37147955
DOI: 10.4103/jcrt.jcrt_774_21 -
Frontiers in Cellular Neuroscience 2017Aminoglycosides are potent antibiotics deployed worldwide despite their known side-effect of sensorineural hearing loss. The main etiology of this sensory deficit is... (Review)
Review
Aminoglycosides are potent antibiotics deployed worldwide despite their known side-effect of sensorineural hearing loss. The main etiology of this sensory deficit is death of inner ear sensory hair cells selectively triggered by aminoglycosides. For decades, research has sought to unravel the molecular events mediating sensory cell demise, emphasizing the roles of reactive oxygen species and their potentials as therapeutic targets. Studies in recent years have revealed candidate transport pathways including the mechanotransducer channel for drug entry into sensory cells. Once inside sensory cells, intracellular targets of aminoglycosides, such as the mitochondrial ribosomes, are beginning to be elucidated. Based on these results, less ototoxic aminoglycoside analogs are being generated and may serve as alternate antimicrobial agents. In this article, we review the latest findings on mechanisms of aminoglycoside entry into hair cells, their intracellular actions and potential therapeutic targets for preventing aminoglycoside ototoxicity.
PubMed: 29093664
DOI: 10.3389/fncel.2017.00325 -
Otolaryngologia Polska = the Polish... Jun 2024<b><br>Introduction:</b> Immune checkpoint inhibitors (ICIs) and T-cell therapies are a modern, well-established cancer treatment. The priority of... (Review)
Review
<b><br>Introduction:</b> Immune checkpoint inhibitors (ICIs) and T-cell therapies are a modern, well-established cancer treatment. The priority of oncological treatment is to cure cancer. However, treatment-related toxicities, i.e. immune-related adverse events (irAEs), continue to emerge and are not that well understood yet. ICIs can cause profound, multiple, and diverse irAEs - the sequelae of unknown mechanisms. One of the organs susceptible to collateral damage is the hearing organ. Complications related to hearing, tinnitus, and balance disorders are extremely burdensome and significantly impair many aspects of the quality of life of patients and survivors.</br> <b><br>Aim:</b> The aim of the work is to review the literature in the area of ototoxicity of ICIs.</br> <b><br>Materials and method:</b> A systematic search of the Web of Science, PubMed, and Embase databases for studies published until 1 March 2022 was conducted.</br> <b><br>Results:</b> Reported clinical symptoms ranged from sudden bilateral hearing loss and imbalance to mild hearing loss or tinnitus with preserved hearing. It was found that the median time from ICI initiation to hearing loss development was 3 months. The hearing impairment was secondary to bilateral sensorineural hearing loss in the majority of patients (>60%), and at least one other irAE accompanied the hearing loss in 2/3 of patients. Hearing loss significantly improved in 45.7% of the patients.</br> <b><br>Conclusions:</b> The majority of cases of ICI-related hearing loss presented in the literature were reversible. Therefore, it is important to develop and implement routine therapeutic algorithms. Further research is needed to define the true prevalence of ICI-related hearing loss, optimal diagnostics, and management.</br>.
Topics: Humans; Immune Checkpoint Inhibitors; Ototoxicity; Male; Female; Hearing Loss; Neoplasms; Middle Aged
PubMed: 38808639
DOI: No ID Found -
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