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Agomelatine Attenuates Isoflurane-Induced Inflammation and Damage in Brain Endothelial Cells
BACKGROUND AND PURPOSE: Neurotoxicity of anesthetics has been widely observed by clinicians. It is reported that inflammation and oxidative stress are involved in the pathological process. In the present study, we aimed to assess the therapeutic effects of agomelatine against isoflurane-induced infl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755371/ https://www.ncbi.nlm.nih.gov/pubmed/33376303 http://dx.doi.org/10.2147/DDDT.S281582 |
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author | Cheng, Fang Chang, Huanxian Yan, Fengfeng Yang, Aixing Liu, Jing Liu, Yuliang |
author_facet | Cheng, Fang Chang, Huanxian Yan, Fengfeng Yang, Aixing Liu, Jing Liu, Yuliang |
author_sort | Cheng, Fang |
collection | PubMed |
description | BACKGROUND AND PURPOSE: Neurotoxicity of anesthetics has been widely observed by clinicians. It is reported that inflammation and oxidative stress are involved in the pathological process. In the present study, we aimed to assess the therapeutic effects of agomelatine against isoflurane-induced inflammation and damage to brain endothelial cells. MATERIALS AND METHODS: MTT assay was used to detect cell viability in order to determine the optimized concentration of agomelatine. The bEnd.3 brain endothelial cells were treated with 2% isoflurane in the presence or absence of agomelatine (5, 10 μM) for 24 h. LDH release was evaluated and the ROS levels were checked using DHE staining assay. The expressions of IL-6, IL-8, TNF-α, VEGF, TF, VCAM-1, and ICAM-1 were evaluated using real-time PCR and ELISA. Real-time PCR and Western blot analysis were used to determine the expression level of Egr-1. RESULTS: The decreased cell viability promoted LDH release and elevated ROS levels induced by isoflurane were significantly reversed by the introduction of agomelatine in a dose-dependent manner. The expression levels of IL-6, IL-8, TNF-α, VEGF, TF, VCAM-1, and ICAM-1 were elevated by stimulation with isoflurane, which were significantly suppressed by the administration of agomelatine. The up-regulation of transcriptional factor Egr-1 induced by isoflurane was down-regulated by agomelatine. CONCLUSION: Agomelatine might attenuate isoflurane-induced inflammation and damage via down-regulating Egr-1 in brain endothelial cells. |
format | Online Article Text |
id | pubmed-7755371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-77553712020-12-28 Agomelatine Attenuates Isoflurane-Induced Inflammation and Damage in Brain Endothelial Cells Cheng, Fang Chang, Huanxian Yan, Fengfeng Yang, Aixing Liu, Jing Liu, Yuliang Drug Des Devel Ther Original Research BACKGROUND AND PURPOSE: Neurotoxicity of anesthetics has been widely observed by clinicians. It is reported that inflammation and oxidative stress are involved in the pathological process. In the present study, we aimed to assess the therapeutic effects of agomelatine against isoflurane-induced inflammation and damage to brain endothelial cells. MATERIALS AND METHODS: MTT assay was used to detect cell viability in order to determine the optimized concentration of agomelatine. The bEnd.3 brain endothelial cells were treated with 2% isoflurane in the presence or absence of agomelatine (5, 10 μM) for 24 h. LDH release was evaluated and the ROS levels were checked using DHE staining assay. The expressions of IL-6, IL-8, TNF-α, VEGF, TF, VCAM-1, and ICAM-1 were evaluated using real-time PCR and ELISA. Real-time PCR and Western blot analysis were used to determine the expression level of Egr-1. RESULTS: The decreased cell viability promoted LDH release and elevated ROS levels induced by isoflurane were significantly reversed by the introduction of agomelatine in a dose-dependent manner. The expression levels of IL-6, IL-8, TNF-α, VEGF, TF, VCAM-1, and ICAM-1 were elevated by stimulation with isoflurane, which were significantly suppressed by the administration of agomelatine. The up-regulation of transcriptional factor Egr-1 induced by isoflurane was down-regulated by agomelatine. CONCLUSION: Agomelatine might attenuate isoflurane-induced inflammation and damage via down-regulating Egr-1 in brain endothelial cells. Dove 2020-12-18 /pmc/articles/PMC7755371/ /pubmed/33376303 http://dx.doi.org/10.2147/DDDT.S281582 Text en © 2020 Cheng et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Cheng, Fang Chang, Huanxian Yan, Fengfeng Yang, Aixing Liu, Jing Liu, Yuliang Agomelatine Attenuates Isoflurane-Induced Inflammation and Damage in Brain Endothelial Cells |
title | Agomelatine Attenuates Isoflurane-Induced Inflammation and Damage in Brain Endothelial Cells |
title_full | Agomelatine Attenuates Isoflurane-Induced Inflammation and Damage in Brain Endothelial Cells |
title_fullStr | Agomelatine Attenuates Isoflurane-Induced Inflammation and Damage in Brain Endothelial Cells |
title_full_unstemmed | Agomelatine Attenuates Isoflurane-Induced Inflammation and Damage in Brain Endothelial Cells |
title_short | Agomelatine Attenuates Isoflurane-Induced Inflammation and Damage in Brain Endothelial Cells |
title_sort | agomelatine attenuates isoflurane-induced inflammation and damage in brain endothelial cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755371/ https://www.ncbi.nlm.nih.gov/pubmed/33376303 http://dx.doi.org/10.2147/DDDT.S281582 |
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