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Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats

Obstructive sleep apnea (OSA) can cause intermittent changes in blood oxygen saturation, resulting in the generation of many reactive oxygen species (ROS). To discover new antioxidants and clarify the endoplasmic reticulum (ER) stress involved in cardiac injury in OSA, we established a chronic inter...

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Autores principales: Zhao, Ya-Shuo, An, Ji-Ren, Yang, Shengchang, Guan, Peng, Yu, Fu-Yang, Li, Wenya, Li, Jie-Ru, Guo, Yajing, Sun, Zhi-Min, Ji, En-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431505/
https://www.ncbi.nlm.nih.gov/pubmed/30984338
http://dx.doi.org/10.1155/2019/7415212
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author Zhao, Ya-Shuo
An, Ji-Ren
Yang, Shengchang
Guan, Peng
Yu, Fu-Yang
Li, Wenya
Li, Jie-Ru
Guo, Yajing
Sun, Zhi-Min
Ji, En-Sheng
author_facet Zhao, Ya-Shuo
An, Ji-Ren
Yang, Shengchang
Guan, Peng
Yu, Fu-Yang
Li, Wenya
Li, Jie-Ru
Guo, Yajing
Sun, Zhi-Min
Ji, En-Sheng
author_sort Zhao, Ya-Shuo
collection PubMed
description Obstructive sleep apnea (OSA) can cause intermittent changes in blood oxygen saturation, resulting in the generation of many reactive oxygen species (ROS). To discover new antioxidants and clarify the endoplasmic reticulum (ER) stress involved in cardiac injury in OSA, we established a chronic intermittent hypoxia (CIH) rat model with a fraction of inspired O(2) (FiO(2)) ranging from 21% to 9%, 20 times/h for 8 h/day, and the rats were treated with H(2)-O(2) mixture (67% hydrogen and 33% oxygen) for 2 h/day for 35 days. Our results showed that H(2)-O(2) mixture remarkably improved cardiac dysfunction and myocardial fibrosis. We found that H(2)-O(2) mixture inhalation declined ER stress-induced apoptosis via three major response pathways: PERK-eIF2α-ATF4, IRE 1-XBP1, and ATF 6. Furthermore, we revealed that H(2)-O(2) mixture blocked c-Jun N-terminal kinase- (JNK-) MAPK activation, increased the ratio of Bcl-2/Bax, and inhibited caspase 3 cleavage to protect against CIH-induced cardiac apoptosis. In addition, H(2)-O(2) mixture considerably decreased ROS levels via upregulating superoxide dismutase (SOD) and glutathione (GSH) as well as downregulating NADPH oxidase (NOX 2) expression in the hearts of CIH rats. All the results demonstrated that H(2)-O(2) mixture significantly reduced ER stress and apoptosis and that H(2) might be an efficient antioxidant against the oxidative stress injury induced by CIH.
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spelling pubmed-64315052019-04-14 Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats Zhao, Ya-Shuo An, Ji-Ren Yang, Shengchang Guan, Peng Yu, Fu-Yang Li, Wenya Li, Jie-Ru Guo, Yajing Sun, Zhi-Min Ji, En-Sheng Oxid Med Cell Longev Research Article Obstructive sleep apnea (OSA) can cause intermittent changes in blood oxygen saturation, resulting in the generation of many reactive oxygen species (ROS). To discover new antioxidants and clarify the endoplasmic reticulum (ER) stress involved in cardiac injury in OSA, we established a chronic intermittent hypoxia (CIH) rat model with a fraction of inspired O(2) (FiO(2)) ranging from 21% to 9%, 20 times/h for 8 h/day, and the rats were treated with H(2)-O(2) mixture (67% hydrogen and 33% oxygen) for 2 h/day for 35 days. Our results showed that H(2)-O(2) mixture remarkably improved cardiac dysfunction and myocardial fibrosis. We found that H(2)-O(2) mixture inhalation declined ER stress-induced apoptosis via three major response pathways: PERK-eIF2α-ATF4, IRE 1-XBP1, and ATF 6. Furthermore, we revealed that H(2)-O(2) mixture blocked c-Jun N-terminal kinase- (JNK-) MAPK activation, increased the ratio of Bcl-2/Bax, and inhibited caspase 3 cleavage to protect against CIH-induced cardiac apoptosis. In addition, H(2)-O(2) mixture considerably decreased ROS levels via upregulating superoxide dismutase (SOD) and glutathione (GSH) as well as downregulating NADPH oxidase (NOX 2) expression in the hearts of CIH rats. All the results demonstrated that H(2)-O(2) mixture significantly reduced ER stress and apoptosis and that H(2) might be an efficient antioxidant against the oxidative stress injury induced by CIH. Hindawi 2019-03-07 /pmc/articles/PMC6431505/ /pubmed/30984338 http://dx.doi.org/10.1155/2019/7415212 Text en Copyright © 2019 Ya-Shuo Zhao et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhao, Ya-Shuo
An, Ji-Ren
Yang, Shengchang
Guan, Peng
Yu, Fu-Yang
Li, Wenya
Li, Jie-Ru
Guo, Yajing
Sun, Zhi-Min
Ji, En-Sheng
Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats
title Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats
title_full Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats
title_fullStr Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats
title_full_unstemmed Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats
title_short Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats
title_sort hydrogen and oxygen mixture to improve cardiac dysfunction and myocardial pathological changes induced by intermittent hypoxia in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431505/
https://www.ncbi.nlm.nih.gov/pubmed/30984338
http://dx.doi.org/10.1155/2019/7415212
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