{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:00:44Z","timestamp":1792458044388,"version":"4.5.0"},"reference-count":107,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Victor Babes University of Medicine and Pharmacy, Timi\u0219oara"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Audiology Research"],"abstract":"<jats:p>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\u2019s 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\u2019s efficacy. This review examines the mechanisms of cisplatin-induced ototoxicity, current otoprotective strategies, and emerging approaches to mitigate this adverse effect.<\/jats:p>","DOI":"10.3390\/audiolres15020022","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T05:13:58Z","timestamp":1740633238000},"page":"22","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Strategies to Mitigate Cisplatin-Induced Ototoxicity: A Literature Review of Protective Agents, Mechanisms, and Clinical Gaps"],"prefix":"10.3390","volume":"15","author":[{"given":"Alexandru","family":"Orasan","sequence":"first","affiliation":[{"name":"ENT Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela-Cristina","family":"Negru","sequence":"additional","affiliation":[{"name":"ENT Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anda Ioana","family":"Morgovan","sequence":"additional","affiliation":[{"name":"ENT Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razvan Claudiu","family":"Fleser","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Department, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Sandu","sequence":"additional","affiliation":[{"name":"OncoHelp Cancer Centre, Radiation Oncology Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Str. Rusu Sireanu nr. 34 Timisoara, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian Mihail","family":"Sitaru","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, \u201cLouis Turcanu\u201d Emergency Clinical Hospital for Children, Iosif Nemoianu Street 2, 300011 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4297-077X","authenticated-orcid":false,"given":"Alexandru-Catalin","family":"Motofelea","sequence":"additional","affiliation":[{"name":"Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7755-4608","authenticated-orcid":false,"given":"Nicolae Constantin","family":"Balica","sequence":"additional","affiliation":[{"name":"ENT Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ghosh, S. 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