title: Immunohistochemical localization of OCT2 in the cochlea of various species.
abstract: OBJECTIVE
  To locate the organic cation transporter 2 (OCT2) in the cochlea of three different species and to modulate the ototoxicity of cisplatin in the guinea pig by pretreatment with phenformin, having a known affinity for OCT2.
  
  
  METHODS
  Immunohistochemical and in vivo study.
  
  
  METHODS
  Sections from the auditory end organs were subjected to immunohistochemical staining in order to identify OCT2 in cochlea from untreated rats, guinea pigs, and a pig. In the in vivo study, guinea pigs were given phenformin intravenously 30 minutes before cisplatin administration. Electrophysiological hearing thresholds were determined, and hair cells loss was assessed 96 hours later. The total amount of platinum in cochlear tissue was determined using mass spectrometry.
  
  
  RESULTS
  Organic cation transporter 2 was found in the supporting cells and in type I spiral ganglion cells in the cochlea of all species studied. Pretreatment with phenformin did not reduce the ototoxic side effect of cisplatin. Furthermore, the concentration of platinum in the cochlea was not affected by phenformin.
  
  
  CONCLUSIONS
  The localization of OCT2 in the supporting cells and type I spiral ganglion cells suggests that this transport protein is not primarily involved in cisplatin uptake from the systemic circulation. We hypothesize that OCT2 transport intensifies cisplatin ototoxicity via transport mechanisms in alternate compartments of the cochlea.
  
  
  METHODS
  N/A.
authors.affiliation: Department of Clinical Science, Intervention and Technology.
authors.forename: Victoria
authors.initials: V
authors.lastname: Hellberg
authors.affiliation: Department of Clinical Science, Intervention and Technology.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gahm
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Karolinska Pharmacy, Karolinska University Hospital, Stockholm.
authors.forename: Hans
authors.initials: H
authors.lastname: Ehrsson
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Helge
authors.initials: H
authors.lastname: Rask-Andersen
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Laurell
mesh_terms: D000818:Animals; D003051:Cochlea / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D007150:Immunohistochemistry / Q000379:methods*; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D000075102:Organic Cation Transporter 2; D051381:Rats; D013552:Swine
chemical_list: D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; C491012:Slc22a2 protein, mouse; C100590:Slc22a2 protein, rat
keywords: Cisplatin; OCT2; ototoxicity; phenformin