Strategies to Mitigate Cisplatin-Induced Ototoxicity: A Literature Review of Protective Agents, Mechanisms, and Clinical Gaps
Background: Cisplatin, a widely used chemotherapeutic agent, is associated with significant ototoxicity, leading to progressive and irreversible sensorineural hearing loss in up to 93% of patients. Cisplatin generates reactive oxygen species (ROS) in the cochlea, activating apoptotic and necroptotic...
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2025-02-01
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| author | Alexandru Orasan Mihaela-Cristina Negru Anda Ioana Morgovan Razvan Claudiu Fleser Daniela Sandu Adrian Mihail Sitaru Alexandru-Catalin Motofelea Nicolae Constantin Balica |
| author_facet | Alexandru Orasan Mihaela-Cristina Negru Anda Ioana Morgovan Razvan Claudiu Fleser Daniela Sandu Adrian Mihail Sitaru Alexandru-Catalin Motofelea Nicolae Constantin Balica |
| author_sort | Alexandru Orasan |
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| description | Background: Cisplatin, a widely used chemotherapeutic agent, is associated with significant ototoxicity, leading to progressive and irreversible sensorineural hearing loss in up to 93% of patients. Cisplatin generates reactive oxygen species (ROS) in the cochlea, activating apoptotic and necroptotic pathways that result in hair cell death. Inflammatory processes and nitrative stress also contribute to cochlear damage. Methods: This literature review was conducted to explore the mechanisms underlying cisplatin-induced ototoxicity and evaluate protective strategies, including both current and emerging approaches. A structured search was performed in multiple scientific databases, including PubMed and ScienceDirect, for articles published up to November 2024. Results: Current otoprotective strategies include systemic interventions such as antioxidants, anti-inflammatory agents, and apoptosis inhibitors, as well as localized delivery methods like intratympanic injection and nanoparticle-based systems. However, these approaches have limitations, including potential interference with cisplatin’s antitumor efficacy and systemic side effects. Emerging strategies focus on genetic and biomarker-based risk stratification, novel otoprotective agents targeting alternative pathways, and combination therapies. Repurposed drugs like pravastatin also show promise in reducing cisplatin-induced ototoxicity. Conclusions: Despite these advancements, significant research gaps remain in translating preclinical findings to clinical applications and developing selective otoprotective agents that do not compromise cisplatin’s efficacy. This review examines the mechanisms of cisplatin-induced ototoxicity, current otoprotective strategies, and emerging approaches to mitigate this adverse effect. |
| format | Article |
| id | doaj-art-5b0dfe0ccc2d47379e9d5e6b6cca9323 |
| institution | OA Journals |
| issn | 2039-4349 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | Audiology Research |
| spelling | doaj-art-5b0dfe0ccc2d47379e9d5e6b6cca93232025-08-20T02:17:19ZengMDPI AGAudiology Research2039-43492025-02-011522210.3390/audiolres15020022Strategies to Mitigate Cisplatin-Induced Ototoxicity: A Literature Review of Protective Agents, Mechanisms, and Clinical GapsAlexandru Orasan0Mihaela-Cristina Negru1Anda Ioana Morgovan2Razvan Claudiu Fleser3Daniela Sandu4Adrian Mihail Sitaru5Alexandru-Catalin Motofelea6Nicolae Constantin Balica7ENT Department, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, RomaniaENT Department, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, RomaniaENT Department, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, RomaniaOtorhinolaryngology Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaOncoHelp Cancer Centre, Radiation Oncology Department, “Victor Babes” University of Medicine and Pharmacy, Str. Rusu Sireanu nr. 34 Timisoara, 300041 Timisoara, RomaniaDepartment of Pediatric Surgery, “Louis Turcanu” Emergency Clinical Hospital for Children, Iosif Nemoianu Street 2, 300011 Timisoara, RomaniaCenter for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, RomaniaENT Department, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, RomaniaBackground: Cisplatin, a widely used chemotherapeutic agent, is associated with significant ototoxicity, leading to progressive and irreversible sensorineural hearing loss in up to 93% of patients. Cisplatin generates reactive oxygen species (ROS) in the cochlea, activating apoptotic and necroptotic pathways that result in hair cell death. Inflammatory processes and nitrative stress also contribute to cochlear damage. Methods: This literature review was conducted to explore the mechanisms underlying cisplatin-induced ototoxicity and evaluate protective strategies, including both current and emerging approaches. A structured search was performed in multiple scientific databases, including PubMed and ScienceDirect, for articles published up to November 2024. Results: Current otoprotective strategies include systemic interventions such as antioxidants, anti-inflammatory agents, and apoptosis inhibitors, as well as localized delivery methods like intratympanic injection and nanoparticle-based systems. However, these approaches have limitations, including potential interference with cisplatin’s antitumor efficacy and systemic side effects. Emerging strategies focus on genetic and biomarker-based risk stratification, novel otoprotective agents targeting alternative pathways, and combination therapies. Repurposed drugs like pravastatin also show promise in reducing cisplatin-induced ototoxicity. Conclusions: Despite these advancements, significant research gaps remain in translating preclinical findings to clinical applications and developing selective otoprotective agents that do not compromise cisplatin’s efficacy. This review examines the mechanisms of cisplatin-induced ototoxicity, current otoprotective strategies, and emerging approaches to mitigate this adverse effect.https://www.mdpi.com/2039-4349/15/2/22cisplatinototoxicitychemotherapyantioxidantsnanoparticlesapoptosis |
| spellingShingle | Alexandru Orasan Mihaela-Cristina Negru Anda Ioana Morgovan Razvan Claudiu Fleser Daniela Sandu Adrian Mihail Sitaru Alexandru-Catalin Motofelea Nicolae Constantin Balica Strategies to Mitigate Cisplatin-Induced Ototoxicity: A Literature Review of Protective Agents, Mechanisms, and Clinical Gaps Audiology Research cisplatin ototoxicity chemotherapy antioxidants nanoparticles apoptosis |
| title | Strategies to Mitigate Cisplatin-Induced Ototoxicity: A Literature Review of Protective Agents, Mechanisms, and Clinical Gaps |
| title_full | Strategies to Mitigate Cisplatin-Induced Ototoxicity: A Literature Review of Protective Agents, Mechanisms, and Clinical Gaps |
| title_fullStr | Strategies to Mitigate Cisplatin-Induced Ototoxicity: A Literature Review of Protective Agents, Mechanisms, and Clinical Gaps |
| title_full_unstemmed | Strategies to Mitigate Cisplatin-Induced Ototoxicity: A Literature Review of Protective Agents, Mechanisms, and Clinical Gaps |
| title_short | Strategies to Mitigate Cisplatin-Induced Ototoxicity: A Literature Review of Protective Agents, Mechanisms, and Clinical Gaps |
| title_sort | strategies to mitigate cisplatin induced ototoxicity a literature review of protective agents mechanisms and clinical gaps |
| topic | cisplatin ototoxicity chemotherapy antioxidants nanoparticles apoptosis |
| url | https://www.mdpi.com/2039-4349/15/2/22 |
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