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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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.
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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
title_full A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro
title_fullStr A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro
title_full_unstemmed A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro
title_short A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro
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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