Co-administration of cisplatin and furosemide causes rapid and massive loss of cochlear hair cells in mice.
Co-administration of cisplatin and furosemide causes rapid and massive loss of cochlear hair cells in mice.
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DOI：
10.1007/s12640-011-9244-0
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发表时间：
2011-11
影响因子：
3.7
通讯作者：
Salvi R
中科院分区：
文献类型：
--
作者：
Li Y;Ding D;Jiang H;Fu Y;Salvi R
转基因小鼠的不断扩大为研究耳毒性的生物学机制创造了一个强大的工具。然而，顺铂的耳毒性很难在小鼠身上进行研究，因为它们体型小并且容易因肾毒性而死亡。为了克服这个问题，我们制定了一种通过联合使用呋塞米和袢利尿剂来促进顺铂诱导的耳毒性的策略。一项剂量反应研究确定 200 mg/kg 的呋塞米是破坏血管纹和打开血耳屏障的最佳剂量。我们对纹状体病理学的分析表明，给予顺铂的最佳时间是呋塞米治疗后 1 小时。 0.5 mg/kg 顺铂和 200 mg/kg 呋塞米联合治疗仅导致耳蜗基底 20% 的外毛细胞中度损失，仅有轻度阈值变化，畸变产物耳声发射 (DPOAE) 损失最小。相比之下，1 mg/kg 顺铂加 200 mg/kg 速尿会导致听性脑干反应阈值永久升高 40-50 dB，DPOAE 几乎完全消除，外毛细胞几乎完全丧失。用顺铂加呋塞米治疗的小鼠中发生的广泛的外毛细胞损伤可以作为极其有用的小鼠模型，用于研究外毛细胞再生技术、研究顺铂和呋塞米耳毒性机制以及评估外毛细胞损失对中枢听觉可塑性的感知和电生理后果。
The expanding arsenal of transgenic mice has created a powerful tool for investigating the biological mechanisms involved in ototoxicity. However, cisplatin ototoxicity is difficult to investigate in mice because of their small size and vulnerability to death by nephrotoxicity. To overcome this problem, we developed a strategy for promoting cisplatin-induced ototoxicity by coadministration of furosemide a loop diuretic. A dose–response study identified 200 mg/kg of furosemide as the optimal dose for disrupting the stria vascularis and opening the blood–ear barrier. Our analysis of stria pathology indicated that the optimal period for administering cisplatin was 1 h after furosemide treatment. Combined treatment with 0.5 mg/kg of cisplatin and 200 mg/kg furosemide resulted in only moderate loss of outer hair cells in the basal 20% of the cochlea, only mild threshold shifts and minimal loss of distortion product otoacoustic emission (DPOAE). In contrast, 1 mg/kg of cisplatin plus 200 mg/kg of furosemide resulted in a permanent 40–50 dB elevation of auditory brainstem response thresholds, almost complete elimination of DPOAE, and nearly total loss of outer hair cells. The widespread outer hair cell lesions that develop in mice treated with cisplatin plus furosemide could serve as extremely useful murine model for investigating techniques for regenerating outer hair cells, studying the mechanisms of cisplatin and furosemide ototoxicity and assessing the perceptual and electrophysiological consequences of outer hair cell loss on central auditory plasticity.
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影响因子：
2.8
作者：
Ding, DL;Stracher, A;Salvi, RJ
通讯作者：
Salvi, RJ
DOI：
10.1111/j.1749-6632.1999.tb08640.x
发表时间：
1999-01-01
期刊：
OTOTOXICITY: BASIC SCIENCE AND CLINICAL APPLICATIONS
影响因子：
--
作者：
Ding, DL;Wang, J;Mueller, M
通讯作者：
Mueller, M
影响因子：
2.8
作者：
Coling, Donald E.;Ding, Dalian;Salvi, Richard J.
通讯作者：
Salvi, Richard J.
影响因子：
9.8
作者：
Huang, R. Stephanie;Duan, Shiwei;Dolan, M. Eileen
通讯作者：
Dolan, M. Eileen
太多的好事是：长期使用水杨酸盐治疗可以增强外部毛细胞功能，但会损害听觉神经活动。
影响因子：
2.8
作者：
Chen, Guang-Di;Kermany, Mohammad Habiby;D'Elia, Alessandra;Ralli, Massimo;Tanaka, Chiemi;Bielefeld, Eric C.;Ding, Dalian;Henderson, Donald;Salvi, Richard
通讯作者：
Salvi, Richard