scholarly journals SIRT6‑specific inhibitor OSS‑128167 exacerbates diabetic cardiomyopathy by aggravating inflammation and oxidative stress

2021 ◽  
Vol 23 (5) ◽  
Author(s):  
Yibo Huang ◽  
Junkai Zhang ◽  
Dongdong Xu ◽  
Yu Peng ◽  
Yuan Jin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Specific Inhibitor ◽  
And Oxidative Stress

CTRP3 protects against uric acid-induced endothelial injury by inhibiting inflammation and oxidase stress in rats

2021 ◽  
pp. 153537022110471
Author(s):  
Junxia Zhang ◽  
Xue Lin ◽  
Jinxiu Xu ◽  
Feng Tang ◽  
Lupin Tan
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Specific Inhibitor ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Sprague Dawley ◽  
Protein Levels ◽  
And Oxidative Stress

Hyperuricemia, which contributes to vascular endothelial damage, plays a key role in multiple cardiovascular diseases. This study was designed to investigate whether C1q/tumor necrosis factor (TNF)-related protein 3 (CTRP3) has a protective effect on endothelial damage induced by uric acid and its underlying mechanisms. Animal models of hyperuricemia were established in Sprague-Dawley (SD) rats through the consumption of 10% fructose water for 12 weeks. Then, the rats were given a single injection of Ad-CTRP3 or Ad-GFP. The animal experiments were ended two weeks later. In vitro, human umbilical vein endothelial cells (HUVECs) were first infected with Ad-CTRP3 or Ad-GFP. Then, the cells were stimulated with 10 mg/dL uric acid for 48 h after pretreatment with or without a Toll-like receptor 4 (TLR4)-specific inhibitor. Hyperuricemic rats showed disorganized intimal structures, increased endothelial apoptosis rates, increased inflammatory responses and oxidative stress, which were accompanied by reduced CTRP3 and elevated TLR4 protein levels in the thoracic aorta. In contrast, CTRP3 overexpression decreased TLR4 protein levels and ameliorated inflammatory responses and oxidative stress, thereby improving the morphology and apoptosis of the aortic endothelium in rats with hyperuricemia. Similarly, CTRP3 overexpression decreased TLR4-mediated inflammation, reduced oxidative stress, and rescued endothelial damage induced by uric acid in HUVECs. In conclusion, CTRP3 ameliorates uric acid-induced inflammation and oxidative stress, which in turn protects against endothelial injury, possibly by inhibiting TLR4-mediated inflammation and downregulating oxidative stress.

Diabetic Cardiomyopathy and Oxidative Stress

2014 ◽  
pp. 25-32 ◽  
Author(s):  
Somasundaram Arumugam ◽  
Vengadeshprabhu Karuppagounder ◽  
Rajarajan A. Thandavarayan ◽  
Vigneshwaran Pitchaimani ◽  
Hirohito Sone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
And Oxidative Stress

Diabetic Cardiomyopathy and Oxidative Stress: Role of Antioxidants

2011 ◽  
Vol 9 (4) ◽  
pp. 225-230 ◽  
Author(s):  
Rajarajan A. Thandavarayan ◽  
Vijayasree V. Giridharan ◽  
Kenichi Watanabe ◽  
Tetsuya Konishi
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
And Oxidative Stress

Combined metoprolol and ascorbic acid treatment prevents intrinsic damage to the heart during diabetic cardiomyopathy

2014 ◽  
Vol 92 (10) ◽  
pp. 827-837 ◽  
Author(s):  
Varun Saran ◽  
Vijay Sharma ◽  
Richard Wambolt ◽  
Violet G. Yuen ◽  
Michael Allard ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ascorbic Acid ◽  
Body Mass ◽  
Diabetic Cardiomyopathy ◽  
Rat Heart ◽  
Systolic Dysfunction ◽  
Diabetic Rat ◽  
Metabolic Disturbances ◽  
Β Blocker ◽  
And Oxidative Stress

Metabolic disturbances and oxidative stress have been highlighted as potential causative factors for the development of diabetic cardiomyopathy. The β-blocker metoprolol is known to improve function in the diabetic rat heart and ameliorates the sequelae associated with oxidative stress, without lowering oxidative stress. The antioxidant ascorbic acid is known to improve function in the diabetic rat heart. We tested whether a combination of ascorbic acid and metoprolol treatment would improve function further than each drug individually. Control and streptozotocin-induced diabetic Wistar rats were treated with metoprolol (15 mg·(kg body mass)−1·day−1, via an osmotic pump) and (or) ascorbic acid (1000 mg·(kg body mass)−1·day−1, via their drinking water). To study the effect of treatment on the development of dysfunction, we examined time points before (5 weeks diabetic) and after (7 weeks diabetic) development of overt systolic dysfunction. Echocardiography and working-heart-perfusion were used to assess cardiac function. Blood and tissue samples were collected to assess the severity of disease and oxidative stress. While both drugs improved function, only ascorbic acid had effects on oxidative damage. Combination treatment had a more pronounced improvement in function. Our β-blocker + antioxidant treatment strategy focused on oxidative stress, not diabetes specifically; therefore, it may prove useful in other diseases where oxidative stress contributes to the pathology.

scholarly journals Xinmailong Attenuates Doxorubicin-Induced Lysosomal Dysfunction and Oxidative Stress in H9c2 Cells via HO-1

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yu Jiang ◽  
Yanjuan Liu ◽  
Wen Xiao ◽  
Dandan Zhang ◽  
Xiehong Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Injury ◽  
Specific Inhibitor ◽  
Heme Oxygenase 1 ◽  
H9c2 Cells ◽  
Autophagy Flux ◽  
Sod Activity ◽  
Lysosomal Function ◽  
Lysosomal Dysfunction ◽  
And Oxidative Stress

The clinical use of doxorubicin (DOX) is limited by its cardiotoxicity, which is closely associated with oxidative stress. Xinmailong (XML) is a bioactive peptide extracted from American cockroaches, which has been mainly applied to treat chronic heart failure in China. Our previous study showed that XML attenuates DOX-induced oxidative stress. However, the mechanism of XML in DOX-induced cardiotoxicity remains unclear. Heme oxygenase-1 (HO-1), an enzyme that is ubiquitously expressed in all cell types, has been found to take antioxidant effects in many cardiovascular diseases, and its expression is protectively upregulated under DOX treatment. Lysosome and autophagy are closely involved in oxidative stress as well. It is still unknown whether XML could attenuate doxorubicin-induced lysosomal dysfunction and oxidative stress in H9c2 cells via HO-1. Thus, this study was aimed at investigating the involvement of HO-1-mediated lysosomal function and autophagy flux in DOX-induced oxidative stress and cardiotoxicity in H9c2 cells. Our results showed that XML treatment markedly increased cell proliferation and SOD activity, improved lysosomal function, and ameliorated autophagy flux block in DOX-treated H9c2 cells. Furthermore, XML significantly increased HO-1 expression following DOX treatment. Importantly, HO-1-specific inhibitor (Znpp) or HO-1 siRNA could significantly attenuate the protective effects of XML against DOX-induced cell injury, oxidative stress, lysosomal dysfunction, and autophagy flux block. These results suggest that XML protects against DOX-induced cardiotoxicity through HO-1-mediated recovery of lysosomal function and autophagy flux and decreases oxidative stress, providing a novel mechanism responsible for the protection of XML against DOX-induced cardiomyopathy.

scholarly journals Activation of TGR5 Partially Alleviates High Glucose-Induced Cardiomyocyte Injury by Inhibition of Inflammatory Responses and Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Li Deng ◽  
Xuxin Chen ◽  
Yi Zhong ◽  
Xing Wen ◽  
Ying Cai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Inflammatory Responses ◽  
Inhibitory Effects ◽  
Rt Pcr ◽  
Hoechst 33342 ◽  
Selective Agonist ◽  
Cardioprotective Effects ◽  
And Oxidative Stress

High glucose- (HG-) induced cardiomyocyte injury is the leading cause of diabetic cardiomyopathy, which is associated with the induction of inflammatory responses and oxidative stress. TGR5 plays an important role in the regulation of glucose metabolism. However, whether TGR5 has cardioprotective effects against HG-induced cardiomyocyte injury is unknown. Neonatal mouse cardiomyocytes were isolated and incubated in a HG medium. Protein and mRNA expression was detected by western blotting and RT-PCR, respectively. Cell apoptosis was determined by Hoechst 33342 staining and flow cytometry. After treatment of cells with HG, TGR5-selective agonist INT-777 reduced the increase in expression of proinflammatory cytokines and NF-κB, whereas pretreatment of cells with TGR5 shRNA significantly reduced the inhibitory effects of INT-777. We also found that INT-777 increased the protein expression of Nrf2 and HO-1. In the presence of TGR5 shRNA, the expression of Nrf2 and HO-1 was reduced, indicating that TGR5 may exert an antioxidant effect partially through the Nrf2/HO-1 pathway. Furthermore, INT-777 treatment inhibited HG-induced ROS production and apoptosis that were attenuated in the presence of TGR5 shRNA or ZnPP (HO-1 inhibitor). Activation of TGR5 has cardioprotective effects against HG-induced cardiomyocyte injury and could be a pharmacological target for the treatment of diabetic cardiomyopathy.

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