Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1783405940251295744 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6431505 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhaoyashuo hydrogenandoxygenmixturetoimprovecardiacdysfunctionandmyocardialpathologicalchangesinducedbyintermittenthypoxiainrats AT anjiren hydrogenandoxygenmixturetoimprovecardiacdysfunctionandmyocardialpathologicalchangesinducedbyintermittenthypoxiainrats AT yangshengchang hydrogenandoxygenmixturetoimprovecardiacdysfunctionandmyocardialpathologicalchangesinducedbyintermittenthypoxiainrats AT guanpeng hydrogenandoxygenmixturetoimprovecardiacdysfunctionandmyocardialpathologicalchangesinducedbyintermittenthypoxiainrats AT yufuyang hydrogenandoxygenmixturetoimprovecardiacdysfunctionandmyocardialpathologicalchangesinducedbyintermittenthypoxiainrats AT liwenya hydrogenandoxygenmixturetoimprovecardiacdysfunctionandmyocardialpathologicalchangesinducedbyintermittenthypoxiainrats AT lijieru hydrogenandoxygenmixturetoimprovecardiacdysfunctionandmyocardialpathologicalchangesinducedbyintermittenthypoxiainrats AT guoyajing hydrogenandoxygenmixturetoimprovecardiacdysfunctionandmyocardialpathologicalchangesinducedbyintermittenthypoxiainrats AT sunzhimin hydrogenandoxygenmixturetoimprovecardiacdysfunctionandmyocardialpathologicalchangesinducedbyintermittenthypoxiainrats AT jiensheng hydrogenandoxygenmixturetoimprovecardiacdysfunctionandmyocardialpathologicalchangesinducedbyintermittenthypoxiainrats |