Astragaloside IV Attenuates the Myocardial Injury Caused by Adriamycin by Inhibiting Autophagy

Astragaloside IV (ASIV) is the main active component of Astragalus, and can ameliorate cardiomyocyte hypertrophy, apoptosis and fibrosis. In this experiment, we studied how ASIV reduces the cardiotoxicity caused by adriamycin and protects the heart. To this end, rats were randomly divided into the control, ADR, ADR + ASIV and ASIV groups (n = 6). Echocardiography was used to observe cardiac function, HE staining was used to observe myocardial injury, TUNEL staining was used to observe myocardial cell apoptosis, and immunofluorescence and Western blotting was used to observe relevant proteins expression. Experiments have shown that adriamycin can damage heart function in rats, and increase the cell apoptosis index, autophagy level and oxidative stress level. Further results showed that ADR can inhibit the PI3K/Akt pathway. ASIV treatment can significantly improve the cardiac function of rats treated with ADR and regulate autophagy, oxidative stress and apoptosis. Our findings indicate that ASIV may reduce the heart damage caused by adriamycin by activating the PI3K/Akt pathway.

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Effect of astragaloside IV against rat myocardial cell apoptosis induced by oxidative stress via mitochondrial ATP-sensitive potassium channels

Molecular Medicine Reports ◽

10.3892/mmr.2015.3400 ◽

2012 ◽

Vol 12 (1) ◽

pp. 371-376 ◽

Cited By ~ 14

Author(s):

FENG-YING GUAN ◽

SHI-JIE YANG ◽

JINXIANG LIU ◽

SI-RUI YANG

Keyword(s):

Oxidative Stress ◽

Potassium Channels ◽

Cell Apoptosis ◽

Myocardial Cell ◽

Astragaloside Iv

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Dexmedetomidine Protects against Myocardial Ischemia/Reperfusion Injury by Ameliorating Oxidative Stress and Cell Apoptosis through the Trx1-Dependent Akt Pathway

BioMed Research International ◽

10.1155/2020/8979270 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Zhi-lin Wu ◽

Jacques Robert Jeppe Davis ◽

Yi Zhu

Keyword(s):

Oxidative Stress ◽

Myocardial Ischemia ◽

Cardiac Function ◽

Cell Apoptosis ◽

Ischemia Reperfusion ◽

Cardioprotective Effect ◽

Akt Pathway ◽

Rat Hearts ◽

Myocardial Ischemia Reperfusion ◽

Isolated Rat

Dexmedetomidine (Dex) was reported to reduce oxidative stress and protect against myocardial Ischemia/Reperfusion (I/R) injury. However, the molecular mechanism involved in its antioxidant property is not fully elucidated. The present study was aimed at investigating whether the Trx1/Akt pathway participated in the cardioprotective effect of Dex. In the present study, I/R-induced myocardial injury in isolated rat hearts and OGD/R-induced injury in H9c2 cardiomyocytes were established. Our findings suggested that Dex ameliorated myocardial I/R injury by improving cardiac function, reducing myocardial apoptosis and oxidative stress, which was manifested by increased GSH and SOD contents, decreased ROS level, and MDA generation in both the isolated rat hearts and OGD/R-treated H9C2 cells. More importantly, it was found that the level of Trx1 was preserved, and Akt phosphorylation was significantly upregulated by Dex treatment. However, these effects of Dex were abolished by PX-12 (a specific Trx1 inhibitor) administration. Taken together, this study suggests that Dex plays a protective role in myocardial I/R injury, improves cardiac function, and relieves oxidative stress and cell apoptosis. Furthermore, our results present a novel signaling mechanism that the cardioprotective effect of Dex is at least partly achieved through the Trx1-dependent Akt pathway.

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Dl-3-n-Butylphthalide Promotes Cardiac Function, Inhibit Oxidative Stress and Myocardial Apoptosis of Chronic Heart Failure Mice via Stimulating Nrf2/HO-1 pathway

10.21203/rs.3.rs-834507/v1 ◽

2021 ◽

Author(s):

Zhongyu Wang ◽

Yan Zhang ◽

Chun Yang ◽

Hongliang Yang

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Signaling Pathway ◽

Myocardial Injury ◽

Heart Function ◽

Regulatory Protein ◽

Camp Response Element Binding ◽

Tunel Staining ◽

Coronary Artery Ligation ◽

Artery Ligation

Abstract PurposeHeart failure (HF) continues to threat the human health and plagues the world, however, there are limited effective drugs for HF. We aimed to investigate the protective effect of Dl-3-n-Butylphthalide (NBP) on myocardial injury in heart failure mice, and to study regulation mechanisms with Nrf2/HO-1/Ca2+-SERCA2a axis. MethodsSixty C57BL/6J mice were grouped into five groups using a random number table: sham group (Sham), Heart Failure model group (HF), Heart Failure+ NBP group (HN), Heart Failure+NBP+Nrf2 inhibitor (HNM), Heart Failure+ NBP + calmodulin-dependent protein kinase II (CaMKⅡ) antagonist, KN93 (HNK). The HF mice was prepared using left anterior descending coronary artery ligation. As animal model preparation, the heart function was detected using echocardiography. H&E and MASSON trichrome staining were performed to identify myocardial injury; The apoptosis of myocardial was examined by TUNEL staining assay. The levels of different oxidative stress-related proteins were measured through ELISA assay ; The reactive oxygen species and Nrf2 expression in heart tissue were observed with immunofluorescence assay. The levels of SERCA2a, calmodulin, endoplasmic reticulum stress regulatory protein and Nrf2/HO-1 protein were measured using western blotting. ResultsThe results demonstrated that NBP can significantly promote heart function, relieve the injury and inhibit cell apoptosis, meanwhile, reduce ERS injury in heart failure mice through increasing SERCA2a level and reducing Ca2+ influx. Finally, NBP was demonstrated to reduce CaMKⅡphosphorylation levels and decrease cAMP-response element binding protein phosphorylation levels, which suggested that NBP could also activate Nrf2/HO-1 signaling pathway. ConclusionsThis study identified that NPBs treatment promotes the cardiomyocytes ERS and alleviates myocardial injury in heart failure mice which is related with stimulating Nrf2/HO-1 signaling pathway, regulating Ca2+-SERCA2a and reducing Ca2+ influx.

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SRC-3 Knockout Attenuates Myocardial Injury Induced by Chronic Intermittent Hypoxia in Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6372430 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Wanyu Wang ◽

Hongbo Gu ◽

Weihua Li ◽

Yihua Lin ◽

Xiangyang Yao ◽

...

Keyword(s):

Cell Apoptosis ◽

Intermittent Hypoxia ◽

Myocardial Injury ◽

Adult Mouse ◽

Myocardial Cell ◽

Heart Tissue ◽

Chronic Intermittent Hypoxia ◽

Tunel Staining ◽

Mouse Heart ◽

Cardiac Damage

This study investigated the effects of chronic intermittent hypoxia (CIH), a model of sleep apnea syndrome (SAS), on cardiac function. SRC-3 was extremely lowly expressed in the adult mouse heart tissue, while SRC-3 was highly expressed in the adult mouse heart tissue after CIH, suggesting that SRC-3 is involved in CIH model. We further studied the role of SRC-3 in CIH-induced myocardial injury in mice. Twenty-four healthy Balb/c male mice ( n = 16 , wild type; n = 8 , SRC-3 knockout (SRC3-KO)) were randomly divided into three groups: air control (Ctrl), CIH, and CIH+SRC3-KO. Mice were exposed to CIH for 12 weeks. qRT-PCR was used to evaluate cardiac expression of the following genes: 11HSD1, 11HSD2, GR, MR, COX-2, OPN, NOX2, HIF-1-α, IL-1β, IL-6, iNOS, TNF-α, PC-1, and TGF-β. Enzymatic levels of SOD, CAT, MDA, NOS, and NO in the mouse hearts were determined using commercially available kits. Immunohistochemistry (IHC) was used to evaluate NF-κB expression in cardiac tissues. A transmission electron microscope (TEM) was used to evaluate myocardial ultrastructure. TUNEL staining was used to assess myocardial cell apoptosis. CIH induced cardiac damage, which was ameliorated in the SRC-3 KO mice. CIH significantly increased the heart-to-body weight ratio, expression of all aforementioned genes except 11HSD1, GR, and MR, and increased the levels of MDA, NOS, NO, and NF-κB, which were attenuated in the SRC-3 KO mice. The CIH group had the lowest SOD and CAT levels, which were partially recovered in the CIH+SRC3-KO group. 11HSD2 gene expression was elevated in both the CIH and CIH+SRC3-KO groups compared to the Ctrl group. The CIH group had severe myocardial cell apoptosis and mitochondrial dysfunction, which were alleviated in the CIH+SRC3-KO group. CIH causes cardiac damage through inducing oxidative stress and inflammation. Knockout of SRC-3 ameliorates CIH-induced cardiac damage through antagonizing CIH-triggered molecular changes in cardiac tissue.

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Liguzinediol improved the heart function and inhibited myocardial cell apoptosis in rats with heart failure

Acta Pharmacologica Sinica ◽

10.1038/aps.2014.75 ◽

2014 ◽

Vol 35 (10) ◽

pp. 1257-1264 ◽

Cited By ~ 17

Author(s):

Yu Li ◽

Ping Song ◽

Qing Zhu ◽

Qiu-yi Yin ◽

Jia-wen Ji ◽

...

Keyword(s):

Heart Failure ◽

Cell Apoptosis ◽

Heart Function ◽

Myocardial Cell

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Mixture of MMP-2, MLC, and NOS Inhibitors Affects NO Metabolism and Protects Heart from Cardiac I/R Injury

Cardiology Research and Practice ◽

10.1155/2020/1561478 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Anna Krzywonos-Zawadzka ◽

Aleksandra Franczak ◽

Grzegorz Sawicki ◽

Iwona Bil-Lula

Keyword(s):

Oxidative Stress ◽

Cardiac Function ◽

Ischemia Reperfusion Injury ◽

Ex Vivo ◽

Heart Function ◽

Ischemia Reperfusion ◽

Tissue Expression ◽

Matrix Metalloproteinase 2 ◽

No Production ◽

Nos Inhibitors

Objectives. Coronary reperfusion procedure leads to ischemia/reperfusion injury of the heart (IRI). IRI arises from increased degradation of myosin light chains and increased activity of matrix metalloproteinase 2 (MMP-2). Increased production of toxic peroxynitrite (ONOO−) during oxidative stress is a source of increased nitration/nitrosylation of contractile proteins, which enhance their degradation through MMP-2. Hence, an imbalance in nitric oxide (NO) metabolism along with oxidative stress is an important factor contributing to pathophysiology of cardiovascular disorders, including myocardial infarction. The aim of the current study was to provide an important insight into understanding the interaction of iNOS, eNOS, and ADMA during oxidative stress and to propose the beneficial therapy to modulate this interaction. Material and Methods. Pathogen-free Wistar rats were used in this study as a surrogate heart model ex vivo. Rat hearts perfused using the Langendorff method were subjected to global no-flow ischemia with or without administration of DOXY (1 µM), ML-7 (0.5 µM), and L-NAME (2 µM) mixture. Haemodynamic parameters of heart function, markers of I/R injury, tissue expression of iNOS, eNOS, and phospho-eNOS, asymmetric dimethylarginine, and NO production as well as MMP-2 activity were measured. Results. Mechanical heart function and coronary flow (CF) were decreased in the hearts subjected to I/R. Treatment of the hearts with the tested mixture resulted in a recovery of mechanical function due to decreased activity of MMP‐2. An infusion of Doxy, ML-7, and L-NAME mixture into I/R hearts decreased the expression of iNOS, eNOS, and phospho-eNOS and in consequence reduced ADMA expression. Decreased ADMA production led to enhanced NO synthesis and improvement of cardiac function at 85% of aerobic control. Conclusions. Synergistic effect of the multidrug therapy with the subthreshold doses allows addressing a few pathways of I/R injury simultaneously to achieve protection of cardiac function during I/R.

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