An integrated view of cisplatin-induced nephrotoxicity and ototoxicity

Takatoshi Karasawa; Peter S. Steyger

doi:10.1016/j.toxlet.2015.06.012

An integrated view of cisplatin-induced nephrotoxicity and ototoxicity

Takatoshi Karasawa
, Peter S. Steyger

Otolaryngology

Research output: Contribution to journal › Review article › peer-review

457 Scopus citations

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.

Original language	English (US)
Pages (from-to)	219-227
Number of pages	9
Journal	Toxicology Letters
Volume	237
Issue number	3
DOIs	https://doi.org/10.1016/j.toxlet.2015.06.012
State	Published - Sep 7 2015

Funding

This work was supported by National Institute on Deafness and Other Communication Disorders at the National Institutes of Health (R21 DC010231; R01 DC012588) and Medical Research Foundation of Oregon grants to P.S.S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funders	Funder number
Oregon Medical Research Foundation
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	R01 DC012588
National Institute on Deafness and Other Communication Disorders R01DC012546 Xue Zhong Liu National Institute on Deafness and Other Communication Disorders R01DC012115 Xue Zhong Liu National Institute on Deafness and Other Communication Disorders R01DC014427 Ulrich Müller Peter G Barr-Gillespie National Institute on Deafnessand Other Communication Disorders R01DC005965 Ulrich Müller National Institute on Deafness and Other Communication Disorders	R21DC010231

Keywords

Cisplatin
Intracellular mechanisms
Nephrotoxicity
Ototoxicity

ASJC Scopus subject areas

Toxicology

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10.1016/j.toxlet.2015.06.012

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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.",

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AB - 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.

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An integrated view of cisplatin-induced nephrotoxicity and ototoxicity

Abstract

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Keywords

ASJC Scopus subject areas

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