Comparison of Cochlear Cell Death Caused by Cisplatin, Alone and in Combination with Furosemide
Comparison of Cochlear Cell Death Caused by Cisplatin, Alone and in Combination with Furosemide
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顺铂单独使用以及与呋塞米联用导致耳蜗细胞死亡的比较
DOI：
10.1177/0192623313483213
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发表时间：
2014-02
影响因子：
1.5
通讯作者：
Wang Jian
中科院分区：
文献类型：
--
作者：
Chen Z;Su K;Yin Shankai;Wang Jian
建立合适的动物模型是探讨药物耳毒性机制的重要一步。在本研究中，我们使用豚鼠比较了顺铂在两种给药方案下引起的耳蜗损伤：连续给药和与速尿联合给药。单用速尿的效果也被评估；它被发现会导致暂时性听力损失和对血管纹的可逆性损伤。连续应用顺铂似乎是不利的，因为与使用较小顺铂剂量的联合方案相比，它导致了进行性体重减轻和更高的死亡率。联合用药导致了类似的听力损失和毛细胞损失，但死亡率明显降低。然而，它们的共同给药未能对螺旋神经节神经元(SGN)造成类似的损害，就像在单独接受顺铂的动物身上看到的那样。这一差异表明，联合方案并未模拟临床应用顺铂对耳蜗神经支配的损害。这一差异也表明SGN损害不是由顺铂通过血管纹进入耳蜗所致。
Establishment of appropriate animal models is an important step in exploring the mechanisms of drug-induced ototoxicity. In the present study, using guinea pigs we compared cochlear lesions induced by cisplatin administered in two regimens: consecutive application alone and in combination with furosemide. The effects of furosemide alone were also evaluated; it was found to cause temporary hearing loss and reversible damage to the stria vascularis. Consecutive application of cisplatin alone appeared to be disadvantageous because it resulted in progressive body weight loss and higher mortality compared to the combined regimen, which used a smaller cisplatin dose. The combined regimen resulted in comparable hearing loss and hair cell loss but a markedly lower mortality. However, their coadministration failed to cause similar damage to spiral ganglion neurons (SGN), as seen in animals that received cisplatin alone. This difference suggests that the combined regimen did not mimic the damage to cochlear neuronal innervation caused by the clinical application of cisplatin. The difference also suggests that the SGN lesion is not caused by cisplatin entering the cochlea via the stria vascularis.
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影响因子：
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作者：
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通讯作者：
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