scholarly journals A SGLT2 Inhibitor Dapagliflozin Alleviates Diabetic Cardiomyopathy by Suppressing High Glucose-Induced Oxidative Stress in vivo and in vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu-jie Xing ◽  
Biao-hu Liu ◽  
Shu-jun Wan ◽  
Yi Cheng ◽  
Si-min Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Sglt2 Inhibitor ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
H9c2 Cells ◽  
Myocardial Oxidative Stress

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.

Long noncoding RNA OIP5-AS1 overexpression promotes viability and inhibits high glucose-induced oxidative stress of cardiomyocytes by targeting microRNA-34a/SIRT1 axis in diabetic cardiomyopathy

2020 ◽  
Vol 21 ◽  
Author(s):  
Haiyun Sun ◽  
Chong Wang ◽  
Ying Zhou ◽  
Xingbo Cheng
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
H9c2 Cells ◽  
Promoting Effect

Objective: Diabetic cardiomyopathy (DCM) is an important complication of diabetes. This study was attempted to discover the effects of long noncoding RNA OIP5-AS1 (OIP5-AS1) on the viability and oxidative stress of cardiomyocyte in DCM. Methods: The expression of OIP5-AS1 and microRNA-34a (miR-34a) in DCM was detected by qRT-PCR. In vitro, DCM was simulated by high glucose (HG, 30 mM) treatment in H9c2 cells. The viability of HG (30 mM)-treated H9c2 cells was examined by MTT assay. The reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were used to evaluate the oxidative stress of HG (30 mM)-treated H9c2 cells. Dual-luciferase reporter assay was used to confirm the interactions among OIP5-AS1, miR-34a and SIRT1. Western blot was applied to analyze the protein expression of SIRT1. Results: The expression of OIP5-AS1 was down-regulated in DCM, but miR-34a was up-regulated. The functional experiment stated that OIP5-AS1 overexpression increased the viability and SOD level, while decreased the ROS and MDA levels in HG (30 mM)-treated H9c2 cells. The mechanical experiment confirmed that OIP5-AS1 and SIRT1 were both targeted by miR-34a with the complementary binding sites at 3′UTR. MiR-34a overexpression inhibited the protein expression of SIRT1. In the feedback experiments, miR-34a overexpression or SIRT1 inhibition weakened the promoting effect on viability, and mitigated the reduction effect on oxidative stress caused by OIP5-AS1 overexpression in HG (30 mM)-treated H9c2 cells. Conclusions: OIP5-AS1 overexpression enhanced viability and attenuated oxidative stress of cardiomyocyte via regulating miR-34a/SIRT1 axis in DCM, providing a new therapeutic target for DCM.

scholarly journals Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Kaifeng Li ◽  
Mengen Zhai ◽  
Liqing Jiang ◽  
Fan Song ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Therapeutic Potential ◽  
Ros Generation ◽  
Protective Effects ◽  
Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

scholarly journals Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification

2021 ◽  
Vol 22 (22) ◽  
pp. 12277
Author(s):  
En-Shao Liu ◽  
Nai-Ching Chen ◽  
Tzu-Ming Jao ◽  
Chien-Liang Chen
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Vascular Calcification ◽  
Wistar Rats ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Oxidase Inhibitor ◽  
In Vivo Studies ◽  
Ros Production

Medial vascular calcification has emerged as a key factor contributing to cardiovascular mortality in patients with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs) with osteogenic transdifferentiation play a role in vascular calcification. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors reduce reactive oxygen species (ROS) production and calcified-medium–induced calcification of VSMCs. This study investigates the effects of dextromethorphan (DXM), an NADPH oxidase inhibitor, on vascular calcification. We used in vitro and in vivo studies to evaluate the effect of DXM on artery changes in the presence of hyperphosphatemia. The anti-vascular calcification effect of DXM was tested in adenine-fed Wistar rats. High-phosphate medium induced ROS production and calcification of VSMCs. DXM significantly attenuated the increase in ROS production, the decrease in ATP, and mitochondria membrane potential during the calcified-medium–induced VSMC calcification process (p < 0.05). The protective effect of DXM in calcified-medium–induced VSMC calcification was not further increased by NADPH oxidase inhibitors, indicating that NADPH oxidase mediates the effect of DXM. Furthermore, DXM decreased aortic calcification in Wistar rats with CKD. Our results suggest that treatment with DXM can attenuate vascular oxidative stress and ameliorate vascular calcification.

Abstract 6253: Increased Expression of Thioredoxin Interacting Protein Promotes Oxidative Stress and Contributes to the Pathogenesis Of Diabetic Cardiomyopathy

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kim A Connelly ◽  
Darren J Kelly ◽  
Michael Zhang ◽  
Kerri Thai ◽  
Andrew Advani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
High Glucose ◽  
Diastolic Heart Failure ◽  
Transgenic Rat ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Neonatal Cardiomyocytes

Background: Alterations in the thioredoxin (TRX) antioxidant system have been implicated in the pathogenesis of cardiac injury, particularly in the diabetic setting. While constitutively present, TRX activity is reduced by the presence of its endogenous inhibitor, thioredoxin interacting protein (TxnIP). We hypothesized that by increasing TxnIP, diabetes may reduce TRX activity and contribute to oxidative stress. Methods: Cell culture studies were performed using the H9C2 rat cardiomyoblast cell line and neonatal cardiomyocytes isolated from 1 day old Sprague Dawley rat neonates. In-vivo studies were performed using a hemodynamically-validated rodent model of diabetic diastolic heart failure, the diabetic (mRen-2)27 transgenic rat (Ren-2). Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was used as a measure of oxidative stress. Results: In- vitro, high glucose (25mmol/l) resulted in increased TxnIP mRNA expression in both neonatal cardiomyocytes as well as H92C cells (2.21 ± 0.6 v 1.00 ± 0.19, p<0.05 compared to normoglycaemic conditions) with a 45% reduction in TRX activity (0.11 ± 0.01 v 0.061± 0.003, p<0.01). In-vivo, diabetes led to a 250% rise in TxnIP mRNA expression compared to control (2.54 ± 0.5 v 1.00 ± 0.11, p<0.001) that was accompanied by a three fold rise in urinary 8-OHdG (680 ± 280 v 1395 ± 391 ng/ml, p<0.001). Conclusion: In both the in vitro and in vivo settings, high glucose leads to TxnIP over-expression associated with reduced TRX activity thereby increasing oxidative stress and implicating this system in the pathogenesis of the cardiac dysfunction that characterizes the diabetic state. Pharmacological manipulation of the TRX-TxnIP system may represent a novel target to reduce diabetic complications.

Inhibitory effects of Panax ginseng glycoproteins in models of doxorubicin-induced cardiac toxicity in vivo and in vitro

2021 ◽  
Author(s):  
Yajun Chen ◽  
Lei Wang ◽  
Tianjia Liu ◽  
Zhidong Qiu ◽  
Ye Qiu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Cell Viability ◽  
Panax Ginseng ◽  
Cardiac Toxicity ◽  
H9c2 Cell ◽  
Inhibitory Effects ◽  
Myocardial Oxidative Stress

We investigated the protective effect of PGP against DOX-induced cardiotoxicity in vitro and in vivo. PGP increases H9C2 cell viability and inhibits apoptosis, alleviating DOX-induced myocardial oxidative stress-related cardiotoxicity.

Cadmium Chloride Induces Memory Deficits and Hippocampal Damage by Activating the JNK/p66Shc/NADPH Oxidase Axis

2020 ◽  
Vol 39 (5) ◽  
pp. 477-490
Author(s):  
Attalla Farag El-kott ◽  
Ali S. Alshehri ◽  
Heba S. Khalifa ◽  
Abd-El-karim M. Abd-Lateif ◽  
Mohammad Ali Alshehri ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Cadmium Chloride ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Male Rats ◽  
Hippocampal Damage ◽  
Vitro Experiment ◽  
In Vitro Experiment ◽  
In Vivo Experiment

This study investigated whether the mechanism underlying the neurotoxic effects of cadmium chloride (CdCl2) in rats involves p66Shc. This study comprised an initial in vivo experiment followed by an in vitro experiment. For the in vivo experiment, male rats were orally administered saline (vehicle) or CdCl2 (0.05 mg/kg) for 30 days. Thereafter, spatial and retention memory of rats were tested and their hippocampi were used for biochemical and molecular analyses. For the in vitro experiment, control or p66Shc-deficient hippocampal cells were treated with CdCl2 (25 µM) in the presence or absence of SP600125, a c-Jun N-terminal kinase (JNK) inhibitor. Cadmium chloride impaired the spatial learning and retention memory of rats; depleted levels of glutathione and manganese superoxide dismutase; increased reactive oxygen species (ROS), tumor necrosis factor α, and interleukin 6; and induced nuclear factor kappa B activation. Cadmium chloride also decreased the number of pyramidal cells in the CA1 region and induced severe damage to the mitochondria and endoplasmic reticulum of cells in the hippocampi of rats. Moreover, CdCl2 increased the total unphosphorylated p66Shc, phosphorylated (Ser36) p66Shc, phosphorylated JNK, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, cytochrome c, and cleaved caspase-3. A dose–response increase in cell death, ROS, DNA damage, p66Shc, and NADPH oxidase was also observed in cultured hippocampal cells treated with CdCl2. Of note, all of these biochemical changes were attenuated by silencing p66Shc or inhibiting JNK with SP600125. In conclusion, CdCl2 induces hippocampal ROS generation and apoptosis by promoting the JNK-mediated activation of p66Shc.

scholarly journals The Protective Roles of Estrogen Receptor β in Renal Calcium Oxalate Crystal Formation via Reducing the Liver Oxalate Biosynthesis and Renal Oxidative Stress-Mediated Cell Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Wei Zhu ◽  
Zhijian Zhao ◽  
Fu-Ju Chou ◽  
Li Zuo ◽  
Tongzu Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Estrogen Receptor ◽  
Nadph Oxidase ◽  
Calcium Oxalate ◽  
Cell Lines ◽  
Ros Production ◽  
Crystal Deposition ◽  
Caox Crystal

Females develop kidney stones less frequently than males do. However, it is unclear if this gender difference is related to altered estrogen/estrogen receptor (ER) signaling. Here, we found that ER beta (ERβ) signals could suppress hepatic oxalate biosynthesis via transcriptional upregulation of the glyoxylate aminotransferase (AGT1) expression. Results from multiple in vitro renal cell lines also found that ERβ could function via suppressing the oxalate-induced injury through increasing the reactive oxygen species (ROS) production that led to a decrease of the renal calcium oxalate (CaOx) crystal deposition. Mechanism study results showed that ERβ suppressed oxalate-induced oxidative stress via transcriptional suppression of the NADPH oxidase subunit 2 (NOX2) through direct binding to the estrogen response elements (EREs) on the NOX2 5′ promoter. We further applied two in vivo mouse models with glyoxylate-induced renal CaOx crystal deposition and one rat model with 5% hydroxyl-L-proline-induced renal CaOx crystal deposition. Our data demonstrated that mice lacking ERβ (ERβKO) as well as mice or rats treated with ERβ antagonist PHTPP had increased renal CaOx crystal deposition with increased urinary oxalate excretion and renal ROS production. Importantly, targeting ERβ-regulated NOX2 with the NADPH oxidase inhibitor, apocynin, can suppress the renal CaOx crystal deposition in the in vivo mouse model. Together, results from multiple in vitro cell lines and in vivo mouse/rat models all demonstrate that ERβ may protect against renal CaOx crystal deposition via inhibiting the hepatic oxalate biosynthesis and oxidative stress-induced renal injury.

scholarly journals Mangiferin Attenuates Myocardial Ischemia-Reperfusion Injury via MAPK/Nrf-2/HO-1/NF-κB In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Kun Liu ◽  
Fei Wang ◽  
Shuo Wang ◽  
Wei-Nan Li ◽  
Qing Ye
Keyword(s):  
Oxidative Stress ◽  
Coronary Artery ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
H9c2 Cells ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

The aim of this study was to investigate the cardioprotective effect of mangiferin (MAF) in vitro and in vivo. Oxidative stress and inflammatory injury were detected in coronary artery ligation in rats and also in hypoxia-reoxygenation- (H/R-) induced H9c2 cells. MAF inhibited myocardial oxidative stress and proinflammatory cytokines in rats with coronary artery occlusion. The ST segment of MAF treatment groups also resumed. Triphenyltetrazolium chloride (TTC) staining and pathological analysis showed that MAF could significantly reduce myocardial injury. In vitro data showed that MAF could improve hypoxia/reoxygenation- (H/R-) induced H9c2 cell activity. In addition, MAF could significantly reduce oxidative stress and inflammatory pathway protein expression in H/R-induced H9c2 cells. This study has clarified the protective effects of MAF on myocardial injury and also confirmed that oxidative stress and inflammation were involved in the myocardial ischemia-reperfusion injury (I/R) model.

scholarly journals Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Yan ◽  
Si-Chi Xu ◽  
Chun-Yan Kong ◽  
Xiao-Yang Zhou ◽  
Zhou-Yan Bian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Injury ◽  
Inflammatory Factors ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Myocardial Oxidative Stress

Background. Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice. Methods. To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection. Results. Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-γ (PPAR-γ), and the protective effects of piperine were abolished by the treatment of the PPAR-γ antagonist in vivo and in vitro. Conclusions. Piperine could suppress DOX-related cardiac injury via activation of PPAR-γ in mice.

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