Ototoxicity refers to damage of inner ear structures (i.e., the cochlea and vestibule) and their function (hearing and balance) following exposure to specific in-hospital medications (i.e., aminoglycoside antibiotics, platinum-based drugs), as well as a variety of environmental or occupational exposures (e.g., metals and solvents). This review provides a narrative derived from relevant papers describing factors contributing to (or increasing the risk of) aminoglycoside and cisplatin-induced ototoxicity. We also review current strategies to protect against ototoxicity induced by these indispensable pharmacotherapeutic treatments for life-threatening infections and solid tumors. We end by highlighting several interventional strategies that are currently in development, as well as the diverse challenges that still need to be overcome to prevent drug-induced hearing loss.
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http://dx.doi.org/10.1101/cshperspect.a033548 | DOI Listing |
Int J Mol Sci
December 2024
Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Ansan Hospital, Ansan 15355, Republic of Korea.
While cisplatin is an effective anti-tumor treatment, it induces ototoxicity through mechanisms involving DNA damage, oxidative stress, and programmed cell death. Rho-associated coiled-coil-containing protein kinase (ROCK) is essential for numerous cellular processes, including apoptosis regulation. Studies have suggested that ROCK inhibitors could prevent apoptosis and promote regeneration.
View Article and Find Full Text PDFAntioxidants (Basel)
December 2024
Institute of Pharmacology and Toxicology, Paracelsus Medical University, 5020 Salzburg, Austria.
Cisplatin is an established component of treatment protocols for various solid malignancies but carries a significant potential for serious adverse effects. Ototoxicity from cisplatin treatment is an important dose-limiting toxicity that manifests as bilateral, progressive, irreversible, dose-dependent sensorineural hearing loss, ear pain, tinnitus, and vestibular dysfunction. Despite the recent approval of sodium thiosulphate for the prevention of cisplatin-induced hearing loss (CIHL) in pediatric patients, structured prevention programs are not routinely implemented in most hospitals, and reducing platinum-induced ototoxicity in adults remains an important clinical problem without established treatment options.
View Article and Find Full Text PDFTissue Cell
December 2024
ENT Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. Electronic address:
Background: Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Current solutions for SNHL, including hearing aids, cochlear implants, and hearing assistive devices, do not provide consistent results and fail to address the underlying pathology of hair cell and ganglion cell damage. Stem cell therapy is a cornerstone in regenerative medicine.
View Article and Find Full Text PDFJ Otol
July 2024
Department of Biochemistry and Molecular Biology, and Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, Shandong, PR China.
Objectives: Deletion of gene in mice has been linked to progressive hearing loss and degeneration of cochlear cells. Cisplatin, an antitumor drug, can cause various side effects, including ototoxicity. The aim of this study was to investigate the effects of on cisplatin-induced hearing impairment in mice and to explore the possible mechanism.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, Republic of Korea; School of Life Sciences, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address:
mPTP is a multi-protein complex that opens in mitochondria during cell death. Cisplatin-induced hearing loss is also known to be caused by mPTP opening. Thus, our study evaluated the protective effect of a novel mPTP inhibitor named DBP-iPT against cisplatin-induced hearing loss.
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