{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:38:25Z","timestamp":1792291105977,"version":"4.4.0"},"reference-count":36,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T00:00:00Z","timestamp":1267401600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T00:00:00Z","timestamp":1267401600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T00:00:00Z","timestamp":1579132800000},"content-version":"vor","delay-in-days":3608,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["108539"],"award-info":[{"award-number":["108539"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB487\/A4"],"award-info":[{"award-number":["SFB487\/A4"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ajp.amjpathol.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Pathology"],"published-print":{"date-parts":[[2010,3]]},"DOI":"10.2353\/ajpath.2010.090610","type":"journal-article","created":{"date-parts":[[2010,1,28]],"date-time":"2010-01-28T22:06:37Z","timestamp":1264716397000},"page":"1169-1180","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":395,"title":["Organic Cation Transporter 2 Mediates Cisplatin-Induced Oto- and Nephrotoxicity and Is a Target for Protective Interventions"],"prefix":"10.1016","volume":"176","author":[{"given":"Giuliano","family":"Ciarimboli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Deuster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Knief","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sperling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Holtkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayram","family":"Edemir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Pavenst\u00e4dt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Lanvers-Kaminsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette","family":"am Zehnhoff-Dinnesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred H.","family":"Schinkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Koepsell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heribert","family":"J\u00fcrgens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eberhard","family":"Schlatter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.2353\/ajpath.2010.090610_bib1","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1172\/JCI200215606","article-title":"TNF-\u03b1 mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity","volume":"110","author":"Ramesh","year":"2002","journal-title":"J Clin Invest"},{"key":"10.2353\/ajpath.2010.090610_bib2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ctrv.2006.09.006","article-title":"Molecular mechanisms of resistance and toxicity associated with platinating agents","volume":"33","author":"Rabik","year":"2007","journal-title":"Cancer Treat Rev"},{"key":"10.2353\/ajpath.2010.090610_bib3","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/sj.ki.5002786","article-title":"Cisplatin nephrotoxicity: mechanisms and renoprotective strategies","volume":"73","author":"Pabla","year":"2008","journal-title":"Kidney Int"},{"key":"10.2353\/ajpath.2010.090610_bib4","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1016\/j.ejca.2004.08.002","article-title":"Best practice in assessing ototoxicity in children with cancer","volume":"40","author":"Skinner","year":"2004","journal-title":"Eur J Cancer"},{"key":"10.2353\/ajpath.2010.090610_bib5","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1017\/S002221510700134X","article-title":"Blebs in inner and outer hair cells: a pathophysiological hypothesis","volume":"122","author":"Ramirez-Camacho","year":"2008","journal-title":"J Laryngol Otol"},{"key":"10.2353\/ajpath.2010.090610_bib6","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1124\/mol.108.052381","article-title":"The role of the mammalian copper transporter 1 in the cellular accumulation of platinum-based drugs","volume":"75","author":"Larson","year":"2009","journal-title":"Mol Pharmacol"},{"key":"10.2353\/ajpath.2010.090610_bib7","doi-asserted-by":"crossref","first-page":"F505","DOI":"10.1152\/ajprenal.90545.2008","article-title":"The copper transporter Ctr1 contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity","volume":"296","author":"Pabla","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"10.2353\/ajpath.2010.090610_bib8","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1016\/S0002-9440(10)61234-5","article-title":"Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2","volume":"167","author":"Ciarimboli","year":"2005","journal-title":"Am J Pathol"},{"key":"10.2353\/ajpath.2010.090610_bib9","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1016\/j.bcp.2005.09.020","article-title":"Association between tubular toxicity of cisplatin and expression of organic cation transporter rOCT2 (Slc22a2) in the rat","volume":"70","author":"Yonezawa","year":"2005","journal-title":"Biochem Pharmacol"},{"key":"10.2353\/ajpath.2010.090610_bib10","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1681\/ASN.V134866","article-title":"Gene expression levels and immunolocalization of organic ion transporters in the human kidney","volume":"13","author":"Motohashi","year":"2002","journal-title":"J Am Soc Nephrol"},{"key":"10.2353\/ajpath.2010.090610_bib11","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1007\/s00424-003-1089-9","article-title":"The SLC22 drug transporter family","volume":"447","author":"Koepsell","year":"2004","journal-title":"Pflugers Arch"},{"key":"10.2353\/ajpath.2010.090610_bib12","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s10254-003-0017-x","article-title":"Organic cation transporters","volume":"150","author":"Koepsell","year":"2003","journal-title":"Rev Physiol Biochem Pharmacol"},{"key":"10.2353\/ajpath.2010.090610_bib13","doi-asserted-by":"crossref","first-page":"7902","DOI":"10.1128\/MCB.23.21.7902-7908.2003","article-title":"Deficiency in the organic cation transporters 1 and 2 (Oct1\/Oct2 [Slc22a1\/Slc22a2]) in mice abolishes renal secretion of organic cations","volume":"23","author":"Jonker","year":"2003","journal-title":"Mol Cell Biol"},{"key":"10.2353\/ajpath.2010.090610_bib14","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.brainres.2003.10.071","article-title":"A new method for imaging and 3D reconstruction of mammalian cochlea by fluorescent confocal microscopy","volume":"1000","author":"Hardie","year":"2004","journal-title":"Brain Res"},{"key":"10.2353\/ajpath.2010.090610_bib15","doi-asserted-by":"crossref","first-page":"F1504","DOI":"10.1152\/ajprenal.90754.2008","article-title":"The organic cation transporters OCT1, 2, and 3 mediate high affinity transport of the mutagenic vital dye ethidium in the kidney proximal tubule","volume":"296","author":"Lee","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"10.2353\/ajpath.2010.090610_bib16","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J Immunol Methods"},{"key":"10.2353\/ajpath.2010.090610_bib17","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0022-1759(86)90183-3","article-title":"An improved colorimetric assay for interleukin 2","volume":"93","author":"Tada","year":"1986","journal-title":"J Immunol Methods"},{"key":"10.2353\/ajpath.2010.090610_bib18","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394C(T) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.2353\/ajpath.2010.090610_bib19","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/j.1440-1797.2007.00854.x","article-title":"Identification and quantification of apoptosis in the kidney using morphology, biochemical and molecular markers","volume":"12","author":"Hughes","year":"2007","journal-title":"Nephrology"},{"key":"10.2353\/ajpath.2010.090610_bib20","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1124\/dmd.105.006932","article-title":"Tissue distribution and ontogeny of organic cation transporters in mice","volume":"34","author":"Alnouti","year":"2006","journal-title":"Drug Metab Dispos"},{"key":"10.2353\/ajpath.2010.090610_bib21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/jn\/136.1.21","article-title":"Copper transport protein (Ctr1) levels in mice are tissue specific and dependent on copper status","volume":"136","author":"Kuo","year":"2006","journal-title":"J Nutr"},{"key":"10.2353\/ajpath.2010.090610_bib22","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.bcp.2007.03.004","article-title":"Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity","volume":"74","author":"Yokoo","year":"2007","journal-title":"Biochem Pharmacol"},{"key":"10.2353\/ajpath.2010.090610_bib23","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/j.1523-1755.2004.00720.x","article-title":"Nephrotoxicity of platinum complexes is related to basolateral organic cation transport","volume":"66","author":"Ludwig","year":"2004","journal-title":"Kidney Int"},{"key":"10.2353\/ajpath.2010.090610_bib24","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nrd1691","article-title":"Cellular processing of platinum anticancer drugs","volume":"4","author":"Wang","year":"2005","journal-title":"Nat Rev Drug Discov"},{"key":"10.2353\/ajpath.2010.090610_bib25","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1124\/jpet.106.110346","article-title":"Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1\u20133 and multidrug and toxin extrusion family)","volume":"319","author":"Yonezawa","year":"2006","journal-title":"J Pharmacol Exp Ther"},{"key":"10.2353\/ajpath.2010.090610_bib26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.critrevonc.2004.09.007","article-title":"Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs","volume":"53","author":"Safaei","year":"2005","journal-title":"Crit Rev Oncol Hematol"},{"key":"10.2353\/ajpath.2010.090610_bib27","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1681\/ASN.V125875","article-title":"Cisplatin decreases the abundance of aquaporin water channels in rat kidney","volume":"12","author":"Kim","year":"2001","journal-title":"J Am Soc Nephrol"},{"key":"10.2353\/ajpath.2010.090610_bib28","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1288\/00005537-199109000-00010","article-title":"Cisplatinum ototoxicity in children","volume":"101","author":"Pasic","year":"1991","journal-title":"Laryngoscope"},{"key":"10.2353\/ajpath.2010.090610_bib29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-5955(01)00224-6","article-title":"Differential vulnerability of basal and apical hair cells is based on intrinsic susceptibility to free radicals","volume":"155","author":"Sha","year":"2001","journal-title":"Hear Res"},{"key":"10.2353\/ajpath.2010.090610_bib30","doi-asserted-by":"crossref","first-page":"C1918","DOI":"10.1152\/ajpcell.2000.279.6.C1918","article-title":"Transepithelial resistance can be regulated by the intestinal brush-border Na+\/H+ exchanger NHE3","volume":"279","author":"Turner","year":"2000","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.2353\/ajpath.2010.090610_bib31","doi-asserted-by":"crossref","first-page":"F469","DOI":"10.1152\/ajprenal.00059.2004","article-title":"NHE3 Na+\/H+ exchanger supports proximal tubular protein reabsorption in vivo","volume":"287","author":"Gekle","year":"2004","journal-title":"Am J Physiol Renal Physiol"},{"key":"10.2353\/ajpath.2010.090610_bib32","doi-asserted-by":"crossref","first-page":"8847","DOI":"10.1158\/0008-5472.CAN-06-0769","article-title":"Organic cation transporters are determinants of oxaliplatin cytotoxicity","volume":"66","author":"Zhang","year":"2006","journal-title":"Cancer Res"},{"key":"10.2353\/ajpath.2010.090610_bib33","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.canlet.2005.06.051","article-title":"Implications of genetic polymorphisms in drug transporters for pharmacotherapy","volume":"234","author":"Kerb","year":"2006","journal-title":"Cancer Lett"},{"key":"10.2353\/ajpath.2010.090610_bib34","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1159\/000028292","article-title":"Repeat administration of drugs as a means to assess the genetic component in pharmacological variability","volume":"58","author":"Kalow","year":"1999","journal-title":"Pharmacology"},{"key":"10.2353\/ajpath.2010.090610_bib35","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1080\/00498250701882482","article-title":"Organic cation transporters","volume":"38","author":"Ciarimboli","year":"2008","journal-title":"Xenobiotica"},{"key":"10.2353\/ajpath.2010.090610_bib36","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/clpt.2009.139","article-title":"Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity","volume":"86","author":"Filipski","year":"2009","journal-title":"Clin Pharmacol Ther"}],"container-title":["The American Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944010604312?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944010604312?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T14:06:13Z","timestamp":1757599573000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002944010604312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2010,3]]}},"alternative-id":["S0002944010604312"],"URL":"https:\/\/doi.org\/10.2353\/ajpath.2010.090610","relation":{},"ISSN":["0002-9440"],"issn-type":[{"value":"0002-9440","type":"print"}],"subject":[],"published":{"date-parts":[[2010,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Organic Cation Transporter 2 Mediates Cisplatin-Induced Oto- and Nephrotoxicity and Is a Target for Protective Interventions","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.2353\/ajpath.2010.090610","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2010 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}