title: [Platinum agent-induced nephrotoxicity via organic cation transport system].
abstract: Platinum agents are widely used in cancer chemotherapy. Cisplatin, carboplatin, oxaliplatin and nedaplatin have a common chemical structure consisting of platinum, carrier groups and leaving groups, and undergo the similar mechanism of cytotoxicity. Only cisplatin induces nephrotoxicity, although the molecular mechanism involved is unclear. Organic cation transporter (OCT)/SLC22A, and multidrug and toxin extrusion (MATE)/SLC47A play a role in renal handling of cationic drug in the kidney. We focused on a role of transporters in nephrotoxicity of platinum agents. OCT2 mediates the transport of cisplatin and is the determinant of cisplatin-induced nephrotoxicity. In addition, MATE1 protects cisplatin-induced nephrotoxicity. Oxaliplatin, which was a superior substrate of the luminal efflux transporter, MATE2-K as well as OCT2, did not show nephrotoxicity. Moreover, carboplatin and nedaplatin were not transported by these transporters. Substrate specificity could regulate the features of platinum agents. Recent findings indicate that organic cation transporters are key to the nephrotoxicity of platinum agents.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Kyoto, Japan. ayone@kuhp.kyoto-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yonezawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D001693:Biological Transport, Active; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism / Q000502:physiology*; D027702:Organic Cation Transporter 1 / Q000378:metabolism / Q000502:physiology*; D017671:Platinum Compounds / Q000378:metabolism / Q000633:toxicity; D013379:Substrate Specificity
chemical_list: D000970:Antineoplastic Agents; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D017671:Platinum Compounds; C521869:SLC47A1 protein, human; D002945:Cisplatin