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A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro
Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus (DM). One of the hallmarks of the DCM is enhanced oxidative stress in myocardium. The aim of this study was to research the underlying mechanisms involved in the effects of dapagliflozin (Dap) on myocardial oxidative stress...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311522/ https://www.ncbi.nlm.nih.gov/pubmed/34322029 http://dx.doi.org/10.3389/fphar.2021.708177 |
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author | Xing, Yu-jie Liu, Biao-hu Wan, Shu-jun Cheng, Yi Zhou, Si-min Sun, Yue Yao, Xin-ming Hua, Qiang Meng, Xiang-jian Cheng, Jin-han Zhong, Min Zhang, Yan Lv, Kun Kong, Xiang |
author_facet | Xing, Yu-jie Liu, Biao-hu Wan, Shu-jun Cheng, Yi Zhou, Si-min Sun, Yue Yao, Xin-ming Hua, Qiang Meng, Xiang-jian Cheng, Jin-han Zhong, Min Zhang, Yan Lv, Kun Kong, Xiang |
author_sort | Xing, Yu-jie |
collection | PubMed |
description | Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus (DM). One of the hallmarks of the DCM is enhanced oxidative stress in myocardium. The aim of this study was to research the underlying mechanisms involved in the effects of dapagliflozin (Dap) on myocardial oxidative stress both in streptozotocin-induced DCM rats and rat embryonic cardiac myoblasts H9C2 cells exposed to high glucose (33.0 mM). In in vivo studies, diabetic rats were given Dap (1 mg/ kg/ day) by gavage for eight weeks. Dap treatment obviously ameliorated cardiac dysfunction, and improved myocardial fibrosis, apoptosis and oxidase stress. In in vitro studies, Dap also attenuated the enhanced levels of reactive oxygen species and cell death in H9C2 cells incubated with high glucose. Mechanically, Dap administration remarkably reduced the expression of membrane-bound nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits gp91phox and p22phox, suppressed the p67phox subunit translocation to membrane, and decreased the compensatory elevated copper, zinc superoxide dismutase (Cu/Zn-SOD) protein expression and total SOD activity both in vivo and in vitro. Collectively, our results indicated that Dap protects cardiac myocytes from damage caused by hyperglycemia through suppressing NADPH oxidase-mediated oxidative stress. |
format | Online Article Text |
id | pubmed-8311522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83115222021-07-27 A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro Xing, Yu-jie Liu, Biao-hu Wan, Shu-jun Cheng, Yi Zhou, Si-min Sun, Yue Yao, Xin-ming Hua, Qiang Meng, Xiang-jian Cheng, Jin-han Zhong, Min Zhang, Yan Lv, Kun Kong, Xiang Front Pharmacol Pharmacology Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus (DM). One of the hallmarks of the DCM is enhanced oxidative stress in myocardium. The aim of this study was to research the underlying mechanisms involved in the effects of dapagliflozin (Dap) on myocardial oxidative stress both in streptozotocin-induced DCM rats and rat embryonic cardiac myoblasts H9C2 cells exposed to high glucose (33.0 mM). In in vivo studies, diabetic rats were given Dap (1 mg/ kg/ day) by gavage for eight weeks. Dap treatment obviously ameliorated cardiac dysfunction, and improved myocardial fibrosis, apoptosis and oxidase stress. In in vitro studies, Dap also attenuated the enhanced levels of reactive oxygen species and cell death in H9C2 cells incubated with high glucose. Mechanically, Dap administration remarkably reduced the expression of membrane-bound nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits gp91phox and p22phox, suppressed the p67phox subunit translocation to membrane, and decreased the compensatory elevated copper, zinc superoxide dismutase (Cu/Zn-SOD) protein expression and total SOD activity both in vivo and in vitro. Collectively, our results indicated that Dap protects cardiac myocytes from damage caused by hyperglycemia through suppressing NADPH oxidase-mediated oxidative stress. Frontiers Media S.A. 2021-07-12 /pmc/articles/PMC8311522/ /pubmed/34322029 http://dx.doi.org/10.3389/fphar.2021.708177 Text en Copyright © 2021 Xing, Liu, Wan, Cheng, Zhou, Sun, Yao, Hua, Meng, Cheng, Zhong, Zhang, Lv and Kong. 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 | Pharmacology Xing, Yu-jie Liu, Biao-hu Wan, Shu-jun Cheng, Yi Zhou, Si-min Sun, Yue Yao, Xin-ming Hua, Qiang Meng, Xiang-jian Cheng, Jin-han Zhong, Min Zhang, Yan Lv, Kun Kong, Xiang A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro |
title | A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro
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title_full | A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro
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title_fullStr | A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro
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title_full_unstemmed | A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro
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title_short | A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro
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title_sort | sglt2 inhibitor dapagliflozin alleviates diabetic cardiomyopathy by suppressing high glucose-induced oxidative stress in vivo and in vitro |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311522/ https://www.ncbi.nlm.nih.gov/pubmed/34322029 http://dx.doi.org/10.3389/fphar.2021.708177 |
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