Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1784699564036456448 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9065337 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhangqilei tetrandrinepreventsneomycininducedototoxicitybypromotingsteroidbiosynthesis AT wuyunhao tetrandrinepreventsneomycininducedototoxicitybypromotingsteroidbiosynthesis AT yuyan tetrandrinepreventsneomycininducedototoxicitybypromotingsteroidbiosynthesis AT niuyuguang tetrandrinepreventsneomycininducedototoxicitybypromotingsteroidbiosynthesis AT fangqiaojun tetrandrinepreventsneomycininducedototoxicitybypromotingsteroidbiosynthesis AT chenxin tetrandrinepreventsneomycininducedototoxicitybypromotingsteroidbiosynthesis AT qijieyu tetrandrinepreventsneomycininducedototoxicitybypromotingsteroidbiosynthesis AT zhangchen tetrandrinepreventsneomycininducedototoxicitybypromotingsteroidbiosynthesis AT wugeping tetrandrinepreventsneomycininducedototoxicitybypromotingsteroidbiosynthesis AT sukaiming tetrandrinepreventsneomycininducedototoxicitybypromotingsteroidbiosynthesis AT chairenjie tetrandrinepreventsneomycininducedototoxicitybypromotingsteroidbiosynthesis |