title: An integrated view of cisplatin-induced nephrotoxicity and ototoxicity.
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.
authors.affiliation: Oregon Hearing Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Karasawa
authors.affiliation: Oregon Hearing Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States. Electronic address: steygerp@ohsu.edu.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Steyger
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015837:Vestibular Diseases / Q000139:chemically induced / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D002945:Cisplatin
keywords: Cisplatin; Intracellular mechanisms; Nephrotoxicity; Ototoxicity