Cisplatin-induced ototoxicity: Updates on molecular mechanisms and otoprotective strategies

Eur J Pharm Biopharm. 2021 Jun;163:60-71. doi: 10.1016/j.ejpb.2021.03.008. Epub 2021 Mar 26.

Abstract

Cisplatin is a highly effective antitumor drug generally used in the treatment of solid malignant tumors. However, cisplatin causes severe side effects such as bone marrow depression, nephrotoxicity, and ototoxicity, thus limiting its clinical application. The incidence of ototoxicity induced by cisplatin ranges from 20% to 70%, and it usually manifests as a progressive, bilateral and irreversible hearing loss. Although the etiology of cisplatin-induced ototoxicity remains unclear, an increasing body of evidence suggests that the ototoxicity of cisplatin is mainly related to the production of reactive oxygen species and activation of apoptotic pathway in cochlear tissues. Many drugs have been well proved to protect cisplatin-induced hearing loss in vitro and in vivo. However, the anti-tumor effect of cisplatin is also weakened by systemic administration of those drugs for hearing protection, especially antioxidants. Therefore, establishing a local administration strategy contributes to the otoprotection without affecting the effect of cisplatin. This review introduces the pathology of ototoxicity caused by cisplatin, and focuses on recent developments in the mechanisms and protective strategies of cisplatin-induced ototoxicity.

Keywords: Cisplatin; Free radicals; Hearing loss; Ototoxicity.

Publication types

  • Review

MeSH terms

  • Administration, Topical
  • Animals
  • Antineoplastic Agents / adverse effects*
  • Apoptosis / drug effects
  • Cisplatin / adverse effects*
  • Cochlea / drug effects
  • Cochlea / pathology
  • Disease Models, Animal
  • Hearing Loss / chemically induced*
  • Hearing Loss / epidemiology
  • Hearing Loss / pathology
  • Hearing Loss / prevention & control
  • Humans
  • Incidence
  • Neoplasms / drug therapy*
  • Protective Agents / administration & dosage*
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Protective Agents
  • Reactive Oxygen Species
  • Cisplatin