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Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis

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 investigatio...

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Autores principales: Zhang, Qilei, Wu, Yunhao, Yu, Yan, Niu, Yuguang, Fang, Qiaojun, Chen, Xin, Qi, Jieyu, Zhang, Chen, Wu, Geping, Su, Kaiming, Chai, Renjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065337/
https://www.ncbi.nlm.nih.gov/pubmed/35519614
http://dx.doi.org/10.3389/fbioe.2022.876237
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author Zhang, Qilei
Wu, Yunhao
Yu, Yan
Niu, Yuguang
Fang, Qiaojun
Chen, Xin
Qi, Jieyu
Zhang, Chen
Wu, Geping
Su, Kaiming
Chai, Renjie
author_facet Zhang, Qilei
Wu, Yunhao
Yu, Yan
Niu, Yuguang
Fang, Qiaojun
Chen, Xin
Qi, Jieyu
Zhang, Chen
Wu, Geping
Su, Kaiming
Chai, Renjie
author_sort Zhang, Qilei
collection PubMed
description 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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spelling pubmed-90653372022-05-04 Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis Zhang, Qilei Wu, Yunhao Yu, Yan Niu, Yuguang Fang, Qiaojun Chen, Xin Qi, Jieyu Zhang, Chen Wu, Geping Su, Kaiming Chai, Renjie Front Bioeng Biotechnol Bioengineering and Biotechnology 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. Frontiers Media S.A. 2022-04-20 /pmc/articles/PMC9065337/ /pubmed/35519614 http://dx.doi.org/10.3389/fbioe.2022.876237 Text en Copyright © 2022 Zhang, Wu, Yu, Niu, Fang, Chen, Qi, Zhang, Wu, Su and Chai. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Zhang, Qilei
Wu, Yunhao
Yu, Yan
Niu, Yuguang
Fang, Qiaojun
Chen, Xin
Qi, Jieyu
Zhang, Chen
Wu, Geping
Su, Kaiming
Chai, Renjie
Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis
title Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis
title_full Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis
title_fullStr Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis
title_full_unstemmed Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis
title_short Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis
title_sort tetrandrine prevents neomycin-induced ototoxicity by promoting steroid biosynthesis
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065337/
https://www.ncbi.nlm.nih.gov/pubmed/35519614
http://dx.doi.org/10.3389/fbioe.2022.876237
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