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Immunohistochemical localization of OCT2 in the cochlea of various species
Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden..
Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Karolinska Univ Hosp, Karolinska Pharm, S-14186 Stockholm, Sweden..
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2015 (English)In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 125, no 9, E320-E325 p.Article in journal (Refereed) Published
Abstract [en]

ObjectiveTo 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. Study DesignImmunohistochemical and in vivo study. MethodsSections 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. ResultsOrganic 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. ConclusionsThe 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. Level of EvidenceN/A. Laryngoscope, 125:E320-E325, 2015

Place, publisher, year, edition, pages
2015. Vol. 125, no 9, E320-E325 p.
Keyword [en]
Cisplatin, ototoxicity, OCT2, phenformin
National Category
Surgery Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-262970DOI: 10.1002/lary.25304ISI: 000360231700005PubMedID: 25892279OAI: oai:DiVA.org:uu-262970DiVA: diva2:856314
Available from: 2015-09-23 Created: 2015-09-23 Last updated: 2017-12-01Bibliographically approved

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Liu, WeiRask-Andersen, HelgeLaurell, Göran

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