An integrated view of cisplatin-induced nephrotoxicity and ototoxicity

Toxicol Lett. 2015 Sep 17;237(3):219-27. doi: 10.1016/j.toxlet.2015.06.012. Epub 2015 Jun 20.

Abstract

Cisplatin is one of the most widely-used drugs to treat cancers. However, its nephrotoxic and ototoxic side-effects remain major clinical limitations. Recent studies have improved our understanding of the molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. While cisplatin binding to DNA is the major cytotoxic mechanism in proliferating (cancer) cells, nephrotoxicity and ototoxicity appear to result from toxic levels of reactive oxygen species and protein dysregulation within various cellular compartments. In this review, we discuss molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. We also discuss potential clinical strategies to prevent nephrotoxicity and ototoxicity and their current limitations.

Keywords: Cisplatin; Intracellular mechanisms; Nephrotoxicity; Ototoxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Cisplatin / adverse effects*
  • Humans
  • Kidney Diseases / chemically induced
  • Kidney Diseases / pathology*
  • Reactive Oxygen Species / metabolism
  • Vestibular Diseases / chemically induced
  • Vestibular Diseases / pathology*

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Cisplatin