Journal
TOXICOLOGY LETTERS
Volume 237, Issue 3, Pages 219-227Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2015.06.012
Keywords
Cisplatin; Ototoxicity; Nephrotoxicity; Intracellular mechanisms
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Funding
- National Institute on Deafness and Other Communication Disorders at National Institutes of Health [R21 DC010231, R01 DC012588]
- Medical Research Foundation of Oregon
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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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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