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Icariin Treatment Protects Against Gentamicin-Induced Ototoxicity via Activation of the AMPK-SIRT3 Pathway

Ototoxicity is a serious health problem that greatly affects millions of people worldwide. This condition is caused by the entry of aminoglycosides into auditory hair cells, subsequently inducing reactive oxygen species (ROS) production and accumulation. Several strategies have been adopted to overc...

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Autores principales: Hu, Yue, Ma, Xiulan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930742/
https://www.ncbi.nlm.nih.gov/pubmed/33679402
http://dx.doi.org/10.3389/fphar.2021.620741
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author Hu, Yue
Ma, Xiulan
author_facet Hu, Yue
Ma, Xiulan
author_sort Hu, Yue
collection PubMed
description Ototoxicity is a serious health problem that greatly affects millions of people worldwide. This condition is caused by the entry of aminoglycosides into auditory hair cells, subsequently inducing reactive oxygen species (ROS) production and accumulation. Several strategies have been adopted to overcome irreversible ROS-induced hair cell loss in mammals. In recent years, icariin, a major active component of the traditional herb Epimedium, has been widely studied and revealed to have antioxidant, anti-inflammatory, and anti-apoptotic properties. In this study, we found that icariin pretreatment improved the survival rate of gentamicin-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear explants. Icariin remarkably suppressed HEI-OC1 cell apoptosis and inhibited ROS production in cells. Notably, icariin upregulated PGC-1α (SIRT3 promoter) and SIRT3 expression in HEI-OC1 cells. In addition, SIRT3 inhibition significantly attenuated the anti-apoptotic effect of icariin. We also found that icariin can increase AMPK phosphorylation. Further studies showed that inhibition of SIRT3 activity had no significant effect on AMPK phosphorylation. Furthermore, the AMPK inhibitor compound C significantly suppressed SIRT3 expression, meaning that AMPK, as an upstream molecule, regulates SIRT3 expression. Meanwhile, inhibition of AMPK activity significantly reduced the protective effect of icariin on gentamicin ototoxicity. Based on these results, icariin exerts its protective effect on gentamicin-induced ototoxicity via activation of the AMPK-SIRT3 signaling pathway, thus providing a new strategy for treating ototoxicity caused by aminoglycoside antibiotics.
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spelling pubmed-79307422021-03-05 Icariin Treatment Protects Against Gentamicin-Induced Ototoxicity via Activation of the AMPK-SIRT3 Pathway Hu, Yue Ma, Xiulan Front Pharmacol Pharmacology Ototoxicity is a serious health problem that greatly affects millions of people worldwide. This condition is caused by the entry of aminoglycosides into auditory hair cells, subsequently inducing reactive oxygen species (ROS) production and accumulation. Several strategies have been adopted to overcome irreversible ROS-induced hair cell loss in mammals. In recent years, icariin, a major active component of the traditional herb Epimedium, has been widely studied and revealed to have antioxidant, anti-inflammatory, and anti-apoptotic properties. In this study, we found that icariin pretreatment improved the survival rate of gentamicin-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear explants. Icariin remarkably suppressed HEI-OC1 cell apoptosis and inhibited ROS production in cells. Notably, icariin upregulated PGC-1α (SIRT3 promoter) and SIRT3 expression in HEI-OC1 cells. In addition, SIRT3 inhibition significantly attenuated the anti-apoptotic effect of icariin. We also found that icariin can increase AMPK phosphorylation. Further studies showed that inhibition of SIRT3 activity had no significant effect on AMPK phosphorylation. Furthermore, the AMPK inhibitor compound C significantly suppressed SIRT3 expression, meaning that AMPK, as an upstream molecule, regulates SIRT3 expression. Meanwhile, inhibition of AMPK activity significantly reduced the protective effect of icariin on gentamicin ototoxicity. Based on these results, icariin exerts its protective effect on gentamicin-induced ototoxicity via activation of the AMPK-SIRT3 signaling pathway, thus providing a new strategy for treating ototoxicity caused by aminoglycoside antibiotics. Frontiers Media S.A. 2021-02-18 /pmc/articles/PMC7930742/ /pubmed/33679402 http://dx.doi.org/10.3389/fphar.2021.620741 Text en Copyright © 2021 Hu and Ma. http://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 Pharmacology
Hu, Yue
Ma, Xiulan
Icariin Treatment Protects Against Gentamicin-Induced Ototoxicity via Activation of the AMPK-SIRT3 Pathway
title Icariin Treatment Protects Against Gentamicin-Induced Ototoxicity via Activation of the AMPK-SIRT3 Pathway
title_full Icariin Treatment Protects Against Gentamicin-Induced Ototoxicity via Activation of the AMPK-SIRT3 Pathway
title_fullStr Icariin Treatment Protects Against Gentamicin-Induced Ototoxicity via Activation of the AMPK-SIRT3 Pathway
title_full_unstemmed Icariin Treatment Protects Against Gentamicin-Induced Ototoxicity via Activation of the AMPK-SIRT3 Pathway
title_short Icariin Treatment Protects Against Gentamicin-Induced Ototoxicity via Activation of the AMPK-SIRT3 Pathway
title_sort icariin treatment protects against gentamicin-induced ototoxicity via activation of the ampk-sirt3 pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930742/
https://www.ncbi.nlm.nih.gov/pubmed/33679402
http://dx.doi.org/10.3389/fphar.2021.620741
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