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Semin Hear 2019; 40(02): 197-204
DOI: 10.1055/s-0039-1684048
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Mechanisms of Cisplatin-Induced Ototoxicity and Prevention

Leonard P. Rybak
1   Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois
2   Division of Otolaryngology, Southern Illinois University School of Medicine, Springfield, Illinois
,
Debashree Mukherjea
1   Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois
2   Division of Otolaryngology, Southern Illinois University School of Medicine, Springfield, Illinois
,
Vickram Ramkumar
3   Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois
› Author Affiliations
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Publication History

Publication Date:
26 April 2019 (online)

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Abstract

Cisplatin is a highly effective antineoplastic agent used to treat solid tumors. Unfortunately, the administration of this drug leads to significant side effects, including ototoxicity, nephrotoxicity, and neurotoxicity. This review addresses the mechanisms of cisplatin-induced ototoxicity and various strategies tested to prevent this distressing adverse effect. The molecular pathways underlying cisplatin ototoxicity are still being investigated. Cisplatin enters targeted cells in the cochlea through the action of several transporters. Once it enters the cochlea, cisplatin is retained for months to years. It can cause DNA damage, inhibit protein synthesis, and generate reactive oxygen species that can lead to inflammation and apoptosis of outer hair cells, resulting in permanent hearing loss. Strategies to prevent cisplatin ototoxicity have utilized antioxidants, transport inhibitors, G-protein receptor agonists, and anti-inflammatory agents. There are no FDA-approved drugs to prevent cisplatin ototoxicity. It is critical that potential protective agents do not interfere with the antitumor efficacy of cisplatin.

Keywords

cisplatin - otoprotection - antioxidants - apoptosis - cochlea
 

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