scholarly journals Kappa-Opioid Agonist U50,488H-Mediated Protection Against Heart Failure Following Myocardial Ischemia/Reperfusion: Dual Roles of Heme Oxygenase-1

2016 ◽  
Vol 39 (6) ◽  
pp. 2158-2172 ◽  
Author(s):  
Guang Tong ◽  
Ben Zhang ◽  
Xuan Zhou ◽  
Jinbo Zhao ◽  
Zhongchan Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Heme Oxygenase ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Opioid Agonist ◽  
Myocardial Ischemia Reperfusion

Backgrounds/Aims: The selective κ-opioid agonist U50,488H protects heart from myocardial ischemia-reperfusion (MI/R) injury. We examined whether U50,488H is also beneficial for MI/R induced heart failure. Methods: Anesthetized male Sprague-Dawley rats were subjected to 30 min of myocardial ischemia via left anterior descending coronary artery (LAD) occlusion, followed by 4 weeks of reperfusion. Infarct size was examined by Evans blue/triphenyl tetrazolium chloride (TTC) staining. Cardiac function and remodeling were examined by echocardiography and histology. HO-1 gene transcription and expression were measured by RT-PCR and western blot. Results: Compared to vehicle-treated MI/R rats, rats administered a single dose of U50,488H at the beginning of reperfusion exhibited reduced myocardial infarct size, oxidative stress, hypertrophy, and fibrosis, improved mechanical function, and greater neovascularization. U50,488H also increased myocardial heme oxygenase (HO)-1 gene transcription and expression, while pharmacological HO-1 inhibition reversed all protective effects of U50,488H. Furthermore, U50,488H protected control cultured cardiomyoctes against simulated I/R-induced apoptosis but not cultures subjected to shRNA-mediated HO-1 knockdown. Inhibition of HO-1 in the subacute phase of reperfusion reversed the U50,488H-induced increase in neovascularization and suppression of oxidative stress. Finally, U50,488H increased Akt phosphorylation and nuclear translocation of Nrf2, a key HO-1 transcription activator, while inhibition of PI3K-Akt signaling abolished U50,488H-induced Nrf2 nuclear translocation, HO-1 upregulation, and cardioprotection. Conclusion: Activation of HO-1 expression through the PI3K-Akt-Nrf2 pathway may mediate the acute and long-term protective effects of U50,488H against heart failure by enhancing cardiomyocyte survival and neoangiogenesis and by reducing oxidative stress.

Cardioprotective Effects of Saponins from Rhizoma Panacis Majoris on Myocardial Ischemia/Reperfusion Injury via Scavenging Excessive Reactive Oxygen Species

2014 ◽  
Vol 934 ◽  
pp. 165-172
Author(s):  
Cai Hong Bai ◽  
Hai Bo He ◽  
Fan Cheng ◽  
Jun Zhi Wang ◽  
Xiao Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Radical Scavenging ◽  
Protective Effects ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

Saponins from Rhizoma Panacis Majoris (SRPM), the bioactive component inRhizoma Panacis Majoris, were reported to possess protective effects on myocardial injury, but the underlying mechanisms remain poorly understood. This study was performed to investigate the protective effects and possible mechanism of SRPM on myocardial ischemia/reperfusion (I/R) injury in vivo. Cardioprotective effects of SPRM in I/R rats was evaluated by hemodynamic, infarct size, biochemical values, histopathological observations, antioxidative relative gene expressions; And the antioxidant activity of SPRM was studied using DPPH scavenging and β-carotene/linoleic acid tests. In the study, we found that SRPM possessed significant free radical-scavenging activity and considerable antioxidant activity, and significantly improved cardiac function, serum biochemical index and antioxidation level, decreased infarct size, reversed the down-regulated mRNA expressions of the SOD1, SOD2, SOD3 in I/R rats. The studies demonstrated that oxidative stress caused the overgeneration and accumulation of ROS, which was central of myocardial I/R injury. SPRM exerted beneficially cardioprotective effects on myocardial I/R injury, mainly scavenging oxidative stress-triggered overgeneration and accumulation of ROS, alleviating myocardial I/R injury and apoptotic cell death.

scholarly journals AMPK/SIRT1 Pathway is Involved in Arctigenin-Mediated Protective Effects Against Myocardial Ischemia-Reperfusion Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Cheng-Yin Liu ◽  
Yi Zhou ◽  
Tao Chen ◽  
Jing-Chao Lei ◽  
Xue-Jun Jiang
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Arctigenin, one of the active ingredients extracted from Great Burdock (Arctium lappa) Achene, has been found to relieve myocardial infarction injury. However, the specific mechanism of Arctigenin against myocardial infarction remains largely unknown. Here, both acute myocardial ischemia-reperfusion injury (AMI/R) rat model and oxygen glucose deprivation (OGD)-induced myocardial cell injury model were constructed to explore the underlying role of AMPK/SIRT1 pathway in Arctigenin-mediated effects. The experimental data in our study demonstrated that Arctigenin ameliorated OGD-mediated cardiomyocytes apoptosis, inflammation and oxidative stress in a dose-dependent manner. Besides, Arctigenin activated AMPK/SIRT1 pathway and downregulated NF-κB phosphorylation in OGD-treated cardiomyocytes, while inhibiting AMPK or SIRT1 by the Compound C (an AMPK inhibitor) or SIRT1-IN-1 (a SIRT1 inhibitor) significantly attenuated Arctigenin-exerted protective effects on cardiomyocytes. In the animal experiments, Arctigenin improved the heart functions and decreased infarct size of the AMI/R-rats, accompanied with downregulated oxidative stress, inflammation and apoptotic levels in the heart tissues. What’s more, Arctigenin enhanced the AMPK/SIRT1 pathway and repressed NF-κB pathway activation. Taken together, our data indicated that Arctigenin reduced cardiomyocytes apoptosis against AMI/R-induced oxidative stress and inflammation at least via AMPK/SIRT1 pathway.

scholarly journals Honokiol Ameliorates Myocardial Ischemia/Reperfusion Injury in Type 1 Diabetic Rats by Reducing Oxidative Stress and Apoptosis through Activating the SIRT1-Nrf2 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Bin Zhang ◽  
Mengen Zhai ◽  
Buying Li ◽  
Zhenhua Liu ◽  
Kaifeng Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen Species Generation ◽  
Nrf2 Signaling Pathway ◽  
Myocardial Ischemia Reperfusion

Reducing oxidative stress is a crucial therapeutic strategy for ameliorating diabetic myocardial ischemia/reperfusion (MI/R) injury. Honokiol (HKL) acts as an effective cardioprotective agent for its strong antioxidative activity. However, its roles and underlying mechanisms against MI/R injury in type 1 diabetes (T1D) remain unknown. Since SIRT1 and Nrf2 are pivotal regulators in diabetes mellitus patients suffering from MI/R injury, we hypothesized that HKL ameliorates diabetic MI/R injury via the SIRT1-Nrf2 signaling pathway. Streptozotocin-induced T1D rats and high-glucose-treated H9c2 cells were exposed to HKL, with or without administration of the SIRT1 inhibitor EX527, SIRT1 siRNA, or Nrf2 siRNA, and then subjected to I/R operation. We found that HKL markedly improved the postischemic cardiac function, decreased the infarct size, reduced the myocardial apoptosis, and diminished the reactive oxygen species generation. Intriguingly, HKL remarkably activated SIRT1 signaling, enhanced Nrf2 nuclear translocation, increased antioxidative signaling, and decreased apoptotic signaling. However, these effects were largely abolished by EX527 or SIRT1 siRNA. Additionally, our cellular experiments showed that Nrf2 siRNA blunted the cytoprotective effects of HKL, without affecting SIRT1 expression and activity. Collectively, these novel findings indicate that HKL abates MI/R injury in T1D by ameliorating myocardial oxidative damage and apoptosis via the SIRT1-Nrf2 signaling pathway.

scholarly journals Cardioprotective Effect of the Aqueous Extract of Lavender Flower against Myocardial Ischemia/Reperfusion Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Dong Wang ◽  
Xin Guo ◽  
Mingjie Zhou ◽  
Jichun Han ◽  
Bo Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Aqueous Extract ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Myocardial Oxidative Stress ◽  
Myocardial Ischemia Reperfusion

This study was conducted to evaluate the cardioprotective property of the aqueous extract of lavender flower (LFAE). The myocardial ischemia/reperfusion (I/R) injury of rat was prepared by Langendorff retrograde perfusion technology. The heart was preperfused with K-H solution containing LFAE for 10 min before 20 minutes global ischemia, and then the reperfusion with K-H solution was conducted for 45 min. The left ventricular developed pressure (LVDP) and the maximum up/downrate of left ventricular pressure (±dp/dtmax) were recorded by physiological recorder as the myocardial function and the myocardial infarct size was detected by TTC staining. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the effluent were measured to determine the myocardial injury degree. The superoxide anion dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue were detected to determine the oxidative stress degree. The results showed that the pretreatment with LFAE significantly decreased the myocardial infarct size and also decreased the LDH, CK activities, and MDA level, while it increased the LVDP, ±dp/dtmax, SOD activities, and the coronary artery flow. Our findings indicated that LFAE could provide protection for heart against the I/R injury which may be related to the improvement of myocardial oxidative stress states.

scholarly journals Dose-Dependent Effects of Long-Term Administration of Hydrogen Sulfide on Myocardial Ischemia–Reperfusion Injury in Male Wistar Rats: Modulation of RKIP, NF-κB, and Oxidative Stress

2020 ◽  
Vol 21 (4) ◽  
pp. 1415 ◽  
Author(s):  
Sajad Jeddi ◽  
Sevda Gheibi ◽  
Khosrow Kashfi ◽  
Mattias Carlström ◽  
Asghar Ghasemi
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Heart Tissue ◽  
Hemodynamic Parameters ◽  
Myocardial Ischemia Reperfusion ◽  
Dose Dependent ◽  
Intermediate Dose

Decreased circulating levels of hydrogen sulfide (H2S) are associated with higher mortality following myocardial ischemia. This study aimed at determining the long-term dose-dependent effects of sodium hydrosulfide (NaSH) administration on myocardial ischemia-reperfusion (IR) injury. Male rats were divided into control and NaSH groups that were treated for 9 weeks with daily intraperitoneal injections of normal saline or NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg), respectively. At the end of the study, hearts from all rats were isolated and hemodynamic parameters were recorded during baseline and following IR. In isolated hearts, infarct size, oxidative stress indices as well as mRNA expression of H2S-, nitric oxide (NO)-producing enzymes, and inflammatory markers were measured. In heart tissue following IR, low doses of NaSH (0.28 and 0.56 mg/kg) had no effect, whereas an intermediate dose (1.6 mg/kg), improved recovery of hemodynamic parameters, decreased infarct size, and decreased oxidative stress. It also increased expression of cystathionine γ-lyase (CSE), Raf kinase inhibitor protein (RKIP), endothelial NO synthase (eNOS), and neuronal NOS (nNOS), as well as decreased expression of inducible NOS (iNOS) and nuclear factor kappa-B (NF-κB). At the high dose of 5.6 mg/kg, NaSH administration was associated with worse recovery of hemodynamic parameters and increased infarct size as well as increased oxidative stress. This dose also decreased expression of CSE, RKIP, and eNOS and increased expression of iNOS and NF-κB. In conclusion, chronic treatment with NaSH has a U-shaped concentration effect on IR injury in heart tissue. An intermediate dose was associated with higher CSE-derived H2S, lower iNOS-derived NO, lower oxidative stress, and inflammation in heart tissue following IR.

scholarly journals Ophiopogonin D Reduces Myocardial Ischemia-Reperfusion Injury via Upregulating CYP2J3/EETs in Rats

2018 ◽  
Vol 49 (4) ◽  
pp. 1646-1658 ◽  
Author(s):  
Xiaoyan Huang ◽  
Yuguang Wang ◽  
Yi Wang ◽  
Liang Yang ◽  
Jia Wang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion ◽  
Apoptotic Effects

Background/Aims: Epoxyeicosatrienoic acids (EETs) are cytochrome P450 epoxygenase (CYP) metabolites of arachidonic acid and have multiple cardiovascular effects. Ophiopogonin D (OP-D) is an important effective monomeric component in Shenmai injection (SM-I). Both have been reported to have a variety of biological functions, including anti-inflammatory, anti-oxidant, and anti-apoptotic effects. We previously demonstrated that OP-D–mediated cardioprotection involves activation of CYP2J2/3 and enhancement of circulating EETs levels in vitro and can be developed as a novel drug for the therapy of myocardial ischemia-reperfusion (MI/R) injury. We therefore hypothesized that the protective effects of OP-D and SM-I against MI/R injury are associated with increased expression of CYP2J3 and enhanced circulating 11,12-EET levels in vivo. Methods: A rat model of MI/R injury was generated by ligation of the left anterior descending coronary artery for 40 min, followed by reperfusion for 2 h to determine the protective effects and potential mechanisms of OP-D and SM-I. Electrocardiogram and ultrasonic cardiogram were used to evaluate cardiac function; 2,3,5-triphenyltetrazolium chloride was used to measure myocardial infarct size; hematoxylin and eosin staining and transmission electron microscopy were used to observe the morphology of myocardial tissue; and the expression of related proteins in the mechanistic study was observed by western blot analysis. Results: We found that OP-D and SM-I exert protective effects on MI/R injury, including regulation of cardiac function, reduction of lactate dehydrogenase and creatine kinase production, attenuation of myocardial infarct size, and improvement of the recovery of damaged myocardial structures. We found that OP-D and SM-I activate CYP2J3 expression and increase levels of circulating 11,12-EET in MI/R-injured rats. Conclusion: We tested the hypothesis that the cardioprotective effects of OP-D and SM-I on MI/R injury are associated with increased expression of CYP2J3 and enhanced circulating 11,12-EET levels in rats. Taken together, our results show that the effects of OP-D and SM-I were also mediated by the activation of the PI3K/Akt/eNOS signaling pathway, while inhibition of the NF-κB signaling pathway and antioxidant and anti-apoptotic effects were involved in the cardioprotective effects of OP-D and SM-I.

The Protective Effects of Preconditioning With Dioscin on Myocardial Ischemia/Reperfusion-Induced Ventricular Arrhythmias by Increasing Connexin 43 Expression in Rats

2018 ◽  
Vol 24 (3) ◽  
pp. 262-268 ◽  
Author(s):  
Jin Cheng ◽  
Chuang Sun ◽  
Jingyu Zhang ◽  
Qing Zou ◽  
Qimeng Hao ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ventricular Arrhythmias ◽  
Connexin 43 ◽  
Ischemia Reperfusion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Protective Effects ◽  
Arterial Blood ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia–reperfusion (IR) injury is associated with high disability and mortality worldwide. This study was to explore the roles of dioscin in the myocardial IR rats and discover the related molecular mechanisms. Rats were divided into 5 groups: sham, IR, IR + 15 mg/kg dioscin, IR + 30 mg/kg dioscin, and IR + 60 mg/kg dioscin. Heart rate (HR), mean arterial blood pressure (MAP), and rate pressure product (RPP) were evaluated at 10 minutes before ischemia, immediately after ischemia, and at the beginning, middle, and end of reperfusion. Arrhythmia score and myocardial infarct size were examined in rats of all groups. The serum creatine kinase-muscle/brain (CKMB) and cardiac troponin I (cTnI) levels were analyzed via enzyme-linked immunosorbent assay. Protein amount of total connexin 43 (T-Cx43) and phosphorylated connexin 43 (P-Cx43) was evaluated by Western blot. Ischemia reperfusion significantly decreased HR, MAP, and RPP of rats compared to the sham group. However, dioscin significantly attenuated the above phenomena in a dose-dependent manner. Dioscin markedly inhibited IR-induced increase in arrhythmias score, infarct size, and serum CKMB and cTnI levels. In addition, dioscin strikingly induced IR-repressed expression of T-Cx43 and P-Cx43. Our results suggested that dioscin pretreatment exhibited protective effects against myocardial IR injury. Moreover, we found that dioscin attenuated myocardial IR-induced ventricular arrhythmias via upregulating Cx43 expression and activation.

Renal Damage Induced by Myocardial Ischemia Reperfusion in Mouse: Role of Oxidative Stress

2019 ◽  
Author(s):  
Xue Tong ◽  
Hong Zhao ◽  
Xiaomei Lu
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Myocardial Ischemia ◽  
Renal Fibrosis ◽  
Renal Damage ◽  
Antioxidant Activities ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion

The aim of this study was to investigate whether oxidative stress has a role in myocardial ischemia reperfusion induced renal damage. The 30 male C57 mice were divided into control group, myocardial ischemia reperfusion (MIR) group and MnTBAP treatment group. In MIR group, the left coronary artery was occluded for 45minutes and reperfusion for 4 weeks. The same procedure was used for the MnTBAP group, with the additional step of MnTBAP (10mg/kg) administered intraperitoneally for 28 days. Before surgery and 4 weeks later, transthoracic echocardiography was performed and urine protein and albumin were measured. At the end of the time, mice were sacrified and kidneys collected for ROS and fibrosis analysis. The plasma was collected for BUN and SCR determination. It was observed that MIR decreased renal function and increased production of ROS, compelled with renal fibrosis. Administration of MnTBAP reduced production of ROS and renal fibrosis and increased renal function. These findings suggest that the MIR plays a causal role in causing renal injury and the MnTBAP exerts renal-protective effects, probably by its antioxidant activities.

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