Immunohistochemical localization of OCT2 in the cochlea of various species.

Immunohistochemical localization of OCT2 in the cochlea of various species.
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DOI:
10.1002/lary.25304
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发表时间:
2015-09
期刊:
影响因子:
2.6
通讯作者:
Laurell, Goeran
Laurell, Goeran
中科院分区:
医学2区
文献类型:
--
作者:
Hellberg, Victoria;Gahm, Caroline;Liu, Wei;Ehrsson, Hans;Rask-Andersen, Helge;Laurell, Goeran

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在三种不同物种的耳蜗中定位有机阳离子转运蛋白2(OCT 2),并通过用对OCT 2具有已知亲和力的苯丙氨酸预处理来调节顺铂在豚鼠中的耳毒性。免疫组织化学和体内研究。对来自听觉终末器官的切片进行免疫组织化学染色,以鉴定来自未处理大鼠、豚鼠和猪的耳蜗中的OCT 2。在体内研究中,豚鼠在顺铂给药前30分钟静脉内给予非那普利。96小时后测定电生理学听阈,并评估毛细胞损失。使用质谱法测定耳蜗组织中铂的总量。有机阳离子转运蛋白2被发现在支持细胞和I型螺旋神经节细胞在所有物种的耳蜗研究。酚妥拉明预处理不能减轻顺铂的耳毒性副作用。此外,铂在耳蜗中的浓度不受苯乙哌啶的影响。OCT 2在支持细胞和I型螺旋神经节细胞中的定位表明,这种转运蛋白主要不参与体循环中顺铂的摄取。我们假设OCT 2转运通过耳蜗交替隔室的转运机制增强顺铂的耳毒性。N/A.喉镜,125:E320-E325,2015
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. Immunohistochemical and in vivo study. 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. 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. 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. N/A. Laryngoscope, 125:E320–E325, 2015
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