Zhang Qilei, Wu Yunhao, Yu Yan, Niu Yuguang, Fang Qiaojun, Chen Xin, Qi Jieyu, Zhang Chen, Wu Geping, Su Kaiming, Chai Renjie
The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, China.
State Key Laboratory of Bioelectronics, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, China.
Front Bioeng Biotechnol. 2022 Apr 20;10:876237. doi: 10.3389/fbioe.2022.876237. eCollection 2022.
Aminoglycoside antibiotics are widely used for the treatment of serious acute infections, life-threatening sepsis, and , 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 , ameliorated neomycin-induced cochlear hair cell injury. In both and 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.
氨基糖苷类抗生素被广泛用于治疗严重的急性感染、危及生命的败血症等，但所有氨基糖苷类药物都会引起副作用，尤其是不可逆的耳毒性。氨基糖苷类药物耳毒性的潜在机制需要进一步研究，临床上也没有有效的药物。在这里，我们表明汉防己甲素（TET），一种从……中提取的具有生物活性的双苄基异喹啉生物碱，改善了新霉素诱导的耳蜗毛细胞损伤。在体内和体外实验中，我们都发现给予TET能显著改善听觉功能，并减少新霉素暴露后毛细胞的损伤。此外，我们观察到TET可以显著降低新霉素暴露后毛细胞的氧化应激和凋亡。最后，RNA测序分析表明，TET主要通过促进类固醇生物合成来预防新霉素诱导的耳毒性。总的来说，我们的结果提供了药理学证据，表明TET可能是预防氨基糖苷类药物诱导耳毒性的一种有前途的药物。
