Naringin attenuates cisplatin- and aminoglycoside-induced hair cell injury in the zebrafish lateral line via multiple pathways.

Naringin attenuates cisplatin- and aminoglycoside-induced hair cell injury in the zebrafish lateral line via multiple pathways.
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DOI:
10.1111/jcmm.16158
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发表时间:
2021-01
影响因子:
5.3
通讯作者:
Lu Z
Lu Z
中科院分区:
医学2区
文献类型:
--
作者:
Li M;Liu J;Liu D;Duan X;Zhang Q;Wang D;Zheng Q;Bai X;Lu Z

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暴露于耳毒性药物是听力损失的一个重要原因,每年影响约3万名儿童,他们可能有严重的身体,社会和心理功能障碍。顺铂(CP)和氨基糖苷类药物是有效的抗菌药物,它们的应用具有很高的耳毒性的可能性,这是由毛细胞(HC)死亡引起的。在这里,我们描述了类黄酮化合物柚皮苷(Nar)对顺铂和氨基糖苷类药物(包括庆大霉素(GM)和新霉素(Neo))在斑马鱼毛细胞中的耳毒性作用的治疗效果。用Nar(100 - 400 μmol/L)孵育的动物可免受CP(150 - 250 μmol/L)、GM(50 - 150 μmol/L)和Neo(50 - 150 μmol/L)的有害作用。我们还为Nar抗耳毒性的潜在机制提供了证据,包括抗氧化,抗凋亡,促进增殖和毛细胞再生。我们发现,在体内和体外,凋亡和焦亡相关基因的mRNA水平都受到Nar的调控。最后,通过证明Nar不影响CP的抗肿瘤功效和氨基糖苷类的体外抗菌活性,我们强调了其在临床应用中的价值。总之,这些结果揭示了一种新的治疗作用,纳作为耳保护药物对CP和氨基糖苷类的不良反应。
Exposure to ototoxic drugs is a significant cause of hearing loss that affects about 30 thousand children with potentially serious physical, social and psychological dysfunctions every year. Cisplatin (CP) and aminoglycosides are effective antineoplastic or bactericidal drugs, and their application has a high probability of ototoxicity which results from the death of hair cells (HCs). Here, we describe the therapeutic effect of the flavonoid compound naringin (Nar) against ototoxic effects of cisplatin and aminoglycosides include gentamicin (GM) and neomycin (Neo) in zebrafish HCs. Animals incubated with Nar (100‐400 μmol/L) were protected against the pernicious effects of CP (150‐250 μmol/L), GM (50‐150 μmol/L) and Neo (50‐150 μmol/L). We also provide evidence for the potential mechanism of Nar against ototoxicity, including antioxidation, anti‐apoptosis, promoting proliferation and hair cell regeneration. We found that mRNA levels of the apoptotic‐ and pyroptosis‐related genes are regulated by Nar both in vivo and in vitro. Finally, by proving that Nar does not affect the anti‐tumour efficacy of CP and antibacterial activity of aminoglycosides in vitro, we highlight its value in clinical application. In conclusion, these results unravel a novel therapeutic role for Nar as an otoprotective drug against the adverse effects of CP and aminoglycosides.
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