Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis.

Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis.
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粉防己碱通过促进类固醇生物合成来预防新霉素引起的耳毒性

DOI:
10.3389/fbioe.2022.876237
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发表时间:
2022
影响因子:
5.7
通讯作者:
Chai, Renjie
Chai, Renjie
中科院分区:
工程技术2区
文献类型:
--
作者:
Zhang, Qilei;Wu, Yunhao;Yu, Yan;Niu, Yuguang;Fang, Qiaojun;Chen, Xin;Qi, Jieyu;Zhang, Chen;Wu, Geping;Su, Kaiming;Chai, Renjie

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氨基糖苷类抗生素广泛用于治疗严重急性感染、危及生命的脓毒症和结核病,但所有氨基糖苷类抗生素都会引起副作用,尤其是不可逆的耳毒性。氨基糖苷类抗生素耳毒性的机制尚需进一步研究,临床上尚无有效药物。在这里,我们表明粉防己碱(泰特)(一种来自粉防己的生物活性双苄基异喹啉生物碱)可以改善新霉素诱导的耳蜗毛细胞损伤。在体外和体内实验中,我们发现,泰特管理显着改善听觉功能和减少毛细胞损伤后,新霉素暴露。此外,我们观察到泰特可显著降低新霉素暴露后毛细胞的氧化应激和凋亡。最后,RNA-seq分析表明,泰特主要通过促进类固醇生物合成来保护新霉素诱导的耳毒性。总的来说,我们的研究结果提供了药理学证据,表明泰特可能是一种有前途的药物,在预防氨基糖苷类药物诱导的耳毒性。
Aminoglycoside antibiotics are widely used for the treatment of serious acute infections, life-threatening sepsis, and tuberculosis, but all aminoglycosides cause side effects, especially irreversible ototoxicity. The mechanisms underlying the ototoxicity of aminoglycosides need further investigation, and there are no effective drugs in the clinic. Here we showed that tetrandrine (TET), a bioactive bisbenzylisoquinoline alkaloid derived from Stephania tetrandra, ameliorated neomycin-induced cochlear hair cell injury. In both in vitro and in vivo experiments we found that TET administration significantly improved auditory function and reduced hair cell damage after neomycin exposure. In addition, we observed that TET could significantly decrease oxidative stress and apoptosis in hair cells after neomycin exposure. Finally, RNA-seq analysis suggested that TET protected against neomycin-induced ototoxicity mainly by promoting steroid biosynthesis. Collectively, our results provide pharmacological evidence showing that TET may be a promising agent in preventing aminoglycosides-induced ototoxicity.
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