title: The antioxidant edaravone prevents cardiac dysfunction by suppressing oxidative stress in type 1 diabetic rats and in high-glucose-induced injured H9c2 cardiomyoblasts.
abstract: Edaravone, a radical scavenger, has been recognized as a potential protective agent for cardiovascular diseases. However, little is known about the effect of edaravone in cardiac complications associated with diabetes. Here, we have demonstrated that edaravone prevents cardiac dysfunction and apoptosis in the streptozotocin-induced type 1 diabetic rat heart. Mechanistic studies revealed that edaravone treatment improved cardiac function and restored superoxide dismutase levels. In addition, treatment of diabetic animals by edaravone increased protein expressions of sirtuin-1 (SIRT-1), peroxisome proliferator activated receptor γ coactivator α (PGC-1α), nuclear factor like-2 (NRF-2), and B cell lymphoma 2 (Bcl-2), and reduced protein expressions of Bax and Caspase-3 compared to the control group. High glucose incubation resulted in the production of reactive oxygen species (ROS) and cell death. Treatment of high-glucose-incubated H9c2 cells by edaravone reduced ROS production and cell death. In addition, the treatment of high-glucose-incubated H9c2 cells by edaravone increased the activity of antioxidative stress by increasing SIRT-1, PGC-1α, and NRF-2, and this treatment also reduced apoptosis by increasing Bcl-2 expression and reducing Bax and Caspase-3 expressions. Knockdown SIRT-1 with small interferer RNA abolished the effects of edaravone. Overall, our data demonstrated that edaravone may be an effective agent against the development of diabetic cardiomyopathy.
authors.affiliation: a Department of Cardiology, First Hospital of Jilin University, Changchun 130021, China.|b Department of Cardiology, Changchun Central Hospital, Changchun 130051, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ji
authors.affiliation: c Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: d Department of Neurology, First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: e Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Chang
authors.affiliation: b Department of Cardiology, Changchun Central Hospital, Changchun 130051, China.
authors.forename: Junli
authors.initials: J
authors.lastname: Gong
authors.affiliation: e Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wei
authors.affiliation: b Department of Cardiology, Changchun Central Hospital, Changchun 130051, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Li
authors.affiliation: a Department of Cardiology, First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000493:pharmacokinetics / Q000627:therapeutic use; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000494:pharmacology*; D006984:Hypertrophy / Q000188:drug therapy; D007328:Insulin; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D001786:Blood Glucose; D016166:Free Radical Scavengers; D007328:Insulin; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D013482:Superoxide Dismutase; D053148:Caspase 3; D056564:Sirtuin 1; D005947:Glucose; D000077553:Edaravone; D000983:Antipyrine
keywords: apoptose; apoptosis; diabète de type 1; edaravone; oxidative stress; stress oxydatif; type 1 diabetes; édaravone