喹喔啉保护斑马鱼侧线毛细胞免受顺铂和氨基糖苷类的损害。,Scientific Reports

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喹喔啉保护斑马鱼侧线毛细胞免受顺铂和氨基糖苷类的损害。
Scientific Reports ( IF 3.8 ) Pub Date : 2018-Oct-11 , DOI: 10.1038/s41598-018-33520-w
Sonia M. Rocha-Sanchez , Olivia Fuson , Shikha Tarang , Linda Goodman , Umesh Pyakurel , Huizhan Liu , David Z. He , Marisa Zallocchi

毛细胞（HC）的死亡是人类听力和平衡障碍的主要原因。它可能由多种侮辱触发，包括噪音，衰老和某些治疗药物的治疗。随着社会技术的进步，噪声污染的来源和具有耳毒性副作用的药物的使用正在迅速增加，这对我们的听力健康构成了威胁。尽管毒素影响听觉功能的基本机制各不相同，但它们共有常见的细胞内副产物，特别是活性氧的产生。在这里，我们描述了杂环化合物喹喔啉（Qx）对斑马鱼HC中耳毒性损害的治疗作用。用Qx孵育的动物受到保护，免受顺铂和庆大霉素的有害作用，并部分免受新霉素的侵害。在存在Qx的情况下，TUNEL阳性HC的数量减少了。由于Qx不会基于FM1-43的吸收和微音势阻止机械传递通道，因此这意味着Qx的耳保护作用在细胞内水平。总之，这些结果揭示了Qx作为一种耳保护药物的新治疗作用，以对抗顺铂和氨基糖苷的有害副作用，为用这些化合物治疗的患者提供了另一种选择。

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Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage.

Hair cell (HC) death is the leading cause of hearing and balance disorders in humans. It can be triggered by multiple insults, including noise, aging, and treatment with certain therapeutic drugs. As society becomes more technologically advanced, the source of noise pollution and the use of drugs with ototoxic side effects are rapidly increasing, posing a threat to our hearing health. Although the underlying mechanism by which ototoxins affect auditory function varies, they share common intracellular byproducts, particularly generation of reactive oxygen species. Here, we described the therapeutic effect of the heterocyclic compound quinoxaline (Qx) against ototoxic insults in zebrafish HCs. Animals incubated with Qx were protected against the deleterious effects of cisplatin and gentamicin, and partially against neomycin. In the presence of Qx, there was a reduction in the number of TUNEL-positive HCs. Since Qx did not block the mechanotransduction channels, based on FM1-43 uptake and microphonic potentials, this implies that Qx's otoprotective effect is at the intracellular level. Together, these results unravel a novel therapeutic role for Qx as an otoprotective drug against the deleterious side effects of cisplatin and aminoglycosides, offering an alternative option for patients treated with these compounds.

更新日期：2018-10-11

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