scholarly journals Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chao He ◽  
Wei Zhang ◽  
Suobei Li ◽  
Wei Ruan ◽  
Junmei Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Survival Rate ◽  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
Hypoxia Inducible Factor ◽  
Cecal Ligation ◽  
Radical Scavenger ◽  
High Dose ◽  
Beneficial Effects ◽  
Apoptosis And Inflammation

Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF-) 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO-) 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP) with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp.) before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg), after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction.

scholarly journals MG53 Protects against Sepsis-Induced Myocardial Dysfunction by Upregulating Peroxisome Proliferator-Activated Receptor-α

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Xue Han ◽  
Daili Chen ◽  
Ning Liufu ◽  
Fengtao Ji ◽  
Qingshi Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Underlying Mechanism ◽  
Cardiomyocyte Apoptosis ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Myocardial Oxidative Stress

Background. The heart is one of the most commonly affected organs during sepsis. Mitsugumin-53 (MG53) has attracted attention in research due to its cardioprotective function. However, the role of MG53 in sepsis-induced myocardial dysfunction (SIMD) remains unknown. The purpose of this study was to explore the underlying mechanism of MG53 in SIMD and investigate its potential relationship with peroxisome proliferator-activated receptor-α (PPARα). Methods. The cecal ligation and puncture (CLP) model was created to induce SIMD in rats. Protein levels of MG53 and PPARα, cardiac function, cardiomyocyte injury, myocardial oxidative stress and inflammatory indicators, and cardiomyocyte apoptosis were measured at 18 h after CLP. The effects of MG53 on PPARα in SIMD were investigated via preconditioning recombinant human MG53 (rhMG53) and PPARα antagonist GW6471. Results. The expression of MG53 and PPARα sharply decreased in the myocardium at 18 h after CLP. Compared with the sham group, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated oxidative stress indicators and proinflammatory cytokines, and excessive cardiomyocyte apoptosis in the CLP group. Supplementation with rhMG53 enhanced myocardial MG53, increased the survival rate with improved cardiac function, and reduced oxidative stress, inflammation, and myocardial apoptosis, which were associated with PPARα upregulation. Pretreatment with GW6471 abolished the abovementioned protective effects induced by MG53. Conclusions. Both MG53 and PPARα were downregulated after sepsis shock. MG53 supplement protects the heart against SIMD by upregulating PPARα expression. Our results provide a new treatment strategy for SIMD.

scholarly journals Paeoniflorin and Hydroxysafflor Yellow A in Xuebijing Injection Attenuate Sepsis-Induced Cardiac Dysfunction and Inhibit Proinflammatory Cytokine Production

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin-Tong Wang ◽  
Zhen Peng ◽  
Ying-Ying An ◽  
Ting Shang ◽  
Guangxu Xiao ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Cardiac Tissue ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Hydroxysafflor Yellow A ◽  
Sepsis Management ◽  
Xuebijing Injection

Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo. RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1β, and CXCL2.

Effects of high-dose chemotherapy (HDCT) and stem cell transplant (SCT) on cardiac function: A prospective study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7106-7106
Author(s):  
G. Vallabhaneni ◽  
F. Momin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Peripheral Blood Progenitor Cells ◽  
Reparative Effect ◽  
A Prospective Study

7106 Background: The effects of HDCT on Cardiac function have not been well defined. In our experience the deleterious effect of HDCT on cardiac function has been overestimated. There is recent evidence that infused peripheral blood progenitor cells have a reparative effect on the myocardium. We prospectively analyzed cardiac function in adult recipients of HDCT and stem cell transplantation before and 100 days after they received HDCT and SCT. Methods: From 1997 to 2004, 109 adult patients received HDCT and SCT. Of these, 34 were male and 51 were female. 55 patients received autologous SCT and 30 patients received allogeneic SCT from HLA matched siblings. Cardiac function was measured by 2D-ECHO two weeks prior to and 100 days post-HDCT and SCT. HDCT was administered according to standard protocols. An ejection fraction [E.F] of greater than 45% was defined as normal. Post-HDCT E.F decrease was defined as reduction of > 10% from baseline. An increase in the EF of greater than 10% from baseline was considered an improvement in cardiac function. Results: 85 patients were evaluable. Median age was 56 years. Auto SCT: Pre-HDCT E.F was normal in 53 auto- SCT and was < 45% in 2 patients. EF declined by 15 and 20% in 2/53 patients (3.7%) who had a normal E.F at baseline. Neither were symptomatic. There was no change in E.F, in patients who had a decreased E.F at baseline. Allogeneic SCT: Pre-HDCT was normal in 29 patients and was < 45% in 1 patient. Post-HDCT E.F remained unchanged in all 29 patients, who had a normal E.F at baseline. The EF improved to normal in the recipient who had a low EF prior to transplant. Conclusions: There was no significant change in cardiac function after HDCT and SCT by 2D-ECHO. The improvement in cardiac function in one of our allogeneic recipients was quite impressive and long lasting and seemed to coincide with engraftment of healthy donor stem cells suggesting that there may be a role for healthy stem cells in improving myocardial dysfunction. No significant financial relationships to disclose.

scholarly journals Propofol Attenuates Hypoxia-Induced Inflammation in BV2 Microglia by Inhibiting Oxidative Stress and NF-κB/Hif-1α Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaowei Peng ◽  
Chenglong Li ◽  
Wei Yu ◽  
Shuai Liu ◽  
Yushuang Cong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hypoxia Inducible Factor ◽  
Underlying Mechanism ◽  
Beneficial Effects ◽  
Hypoxia Inducible Factor 1 ◽  
B Subunit ◽  
Bv2 Cells ◽  
Total Antioxidant ◽  
Bv2 Microglia ◽  
Interfering Rna

Hypoxia-induced neuroinflammation typically causes neurological damage and can occur during stroke, neonatal hypoxic-ischemic encephalopathy, and other diseases. Propofol is widely used as an intravenous anesthetic. Studies have shown that propofol has antineuroinflammatory effect. However, the underlying mechanism remains to be fully elucidated. Thus, we aimed to investigate the beneficial effects of propofol against hypoxia-induced neuroinflammation and elucidated its potential cellular and biochemical mechanisms of action. In this study, we chose cobalt chloride (CoCl2) to establish a hypoxic model. We found that propofol decreased hypoxia-induced proinflammatory cytokines (TNFα, IL-1β, and IL-6) in BV2 microglia, significantly suppressed the excessive production of reactive oxygen species, and increased the total antioxidant capacity and superoxide dismutase activity. Furthermore, propofol attenuated the hypoxia-induced decrease in mitochondrial membrane potential andy 2 strongly inhibited protein expression of nuclear factor-kappa B (NF-κB) subunit p65 and hypoxia inducible factor-1α (Hif-1α) in hypoxic BV2 cells. To investigate the role of NF-κB p65, specific small interfering RNA (siRNA) against NF-κB p65 were transfected into BV2 cells, followed by exposure to hypoxia for 24 h. Hypoxia-induced Hif-1α production was downregulated after NF-κB p65 silencing. Further, propofol suppressed Hif-1α expression by inhibiting the upregulation of NF-κB p65 after exposure to hypoxia in BV2 microglia. In summary, propofol attenuates hypoxia-induced neuroinflammation, at least in part by inhibiting oxidative stress and NF-κB/Hif-1α signaling.

High Dose Pomegranate Extract Suppresses Neutrophil Myeloperoxidase and Induces Oxidative Stress in a Rat Model of Sepsis

2019 ◽  
Vol 89 (5-6) ◽  
pp. 271-284 ◽  
Author(s):  
Sanaz Tavasoli ◽  
Shahryar Eghtesadi ◽  
Mohamadreza Vafa ◽  
Maziar Moradi-Lakeh ◽  
Alireza Sadeghipour ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Total Antioxidant Status ◽  
Thiobarbituric Acid ◽  
Pomegranate Juice ◽  
High Dose ◽  
Myeloperoxidase Activity ◽  
Sepsis Induction

Abstract. Introduction: The effect of using high dose pomegranate extract on sepsis and its safety is not clarified. Considering the fact that proper immune and inflammatory responses are needed to cope with infection, the aim of current study was to assess the effect of high dose pomegranate extract consumption on oxidative and inflammatory responses after disease induction in rat model of sepsis. Methods: Sepsis was induced by Cecal Ligation and Perforation (CLP) surgery. Adult male Wistar rats were divided into three groups of eight animals: Sham; CLP and POMx [consumed POMx (250 mg of pomegranate fruit extract/kg/day) for four weeks before CLP]. Results: Peritoneal neutrophil myeloperoxidase activity was significantly lower in POMx compared with Sham and CLP groups ( p < 0.01 and p < 0.05, respectively). Although antioxidant enzymes were higher in POMx group after sepsis induction, lower serum total antioxidant status (TAS) (p < 0.01 compared with both CLP and Sham groups) and higher liver thiobarbituric acid reactive species (TBARS) levels were observed in this group ( p < 0.01 and p < 0.05, compared with Sham and CLP groups, respectively). Conclusion: High dose POMx consumption prior to sepsis induction, suppressed the vital function of neutrophils in early hours after sepsis initiation, resulting in higher oxidative stress. These findings indicate that caution should be made in using high dose pomegranate products. The main message of current study is that such useful compounds as antioxidants including pomegranate juice which have beneficial effects on general health status may have detrimental effects if misused or used in high doses.

Isoacteoside Attenuates Septic Acute Lung Injury by Inhibiting Inflammation, Oxidative Stress and Endothelial Hyperpermeability in Mice

2021 ◽  
Author(s):  
Yan-nian Luo ◽  
Nan-nan He ◽  
Juan Xu ◽  
Rui Wang ◽  
Wen Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Survival Rate ◽  
Lung Injury ◽  
Cecal Ligation ◽  
Endothelial Permeability ◽  
Mouse Serum ◽  
Control Group ◽  
Expression Levels ◽  
Endothelial Hyperpermeability

Abstract The present study was aimed to explore the protective role of isoacteoside (ISO) in cecal ligation and puncture (CLP)-induced acute lung injury (ALI) in mice. Mice were divided into the following groups: sham control group, ALI group, and ALI+ISO group, in which mice received 10,50 or 100 mg/kg/day of ISO for 3 days before, 0h and 12h after CLP surgery. In the first experiment, all mice were maintained until 72 h after the CLP operation to calculate the survival rate. In the second experiment, mouse serum and lung and bronchoalveolar lavage fluid (BALF) were collected 24 h after model establishment for detection. The results revealed that ISO significantly improved the ALI associated survival rate, reduced the pathological injury, ALI score, infiltration of inflammatory cells, leakage of cells and proteins into BALF, systemic and local cytokine secretion, and pulmonary oxidative stress. Moreover, ISO significantly inhibited the expression levels of the pro-inflammatory proteins TLR4, MyD88, p-NF-κB p65, p-IKKαβ, and p-IκBα and increased the expression levels of the endothelial permeability related proteins ZO-1, claudin 5 and VE-cadherin. In conclusions, ISO mitigated acute lung injury in mice which was attributed to the capacity of ISO to inhibit inflammation, oxidative stress and endothelial hyperpermeability.

The synthetic pentasaccharide fondaparinux prevents coronary microvascular injury and myocardial dysfunction in the ischemic heart

2008 ◽  
Vol 100 (05) ◽  
pp. 912-919 ◽  
Author(s):  
Steve Lancel ◽  
Brigitte Decoster ◽  
Philippe Asseman ◽  
David Montaigne ◽  
Xavier Marechal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Endothelial Activation ◽  
Perfused Heart ◽  
Beneficial Effects ◽  
Extracellular Signal ◽  
Myocardial Contractile ◽  
Heart Injury

SummaryFondaparinux is a synthetic pentasaccharide with powerful anticoagulant properties, which may also reduce ischemia-reperfusion (I/R) injury in vivo.However,the relative contributions of the anticoagulant and anti-inflammatory activities of fondaparinux to the observed protection are unknown.To address this issue, a crystalloid-perfused heart model was used to assess potential effects of fondaparinux on IR-induced heart injury in the absence of blood. Fondaparinux protects the ischemic myocardium independently of its haemostasis effects. Fondaparinux improved post ischemic myocardial contractile performance and tissue damage. These beneficial effects of fondaparinux may be related to the observed reduction in IR-induced oxidative stress and endothelial activation. In addition, fondaparinux altered NADPH oxidase activity and phosphorylated extracellular signal-regulated kinase (ERK) 1/2, suggesting activation of survival signaling pathways. The present study provides novel information by demonstrating that fondaparinux can attenuate inflammatory responses and oxidative stress in connection with IR heart injury. These findings could represent a potential therapeutic strategy for the prevention of myocardial dysfunction.

scholarly journals Mesenchymal stem cell-derived exosomes protect trabecular meshwork from oxidative stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying-chao Li ◽  
Juan Zheng ◽  
Xi-zi Wang ◽  
Xin Wang ◽  
Wen-jing Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Survival Rate ◽  
Candidate Genes ◽  
Inflammatory Cytokines ◽  
Trabecular Meshwork ◽  
Control Groups ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Trabecular Meshwork Cells ◽  
And Control

AbstractThis study aims to investigate the beneficial effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on trabecular meshwork cells under oxidative stress and predict candidate genes associated with this process. Trabecular meshwork cells were pretreated with BMSC-derived exosomes for 24 h, and exposed to 0.1 mM H2O2 for 6 h. Survival rate of trabecular meshwork cells was measured with CCK-8 assay. Production of intracellular reactive oxygen species (iROS) was measured using a flow cytometer. RT-PCR and ELISA were used to detect mRNA and protein levels of inflammatory cytokines and matrix metalloproteinases (MMPs). Sequencing of RNA and miRNA for trabecular meshwork cells from Exo and control groups was performed on BGISEQ500 platform. Phenotypically, pretreatment of BMSC-derived exosomes improves survival rate of trabecular meshwork cells exposed to H2O2, reduces production of iROS, and inhibits expression of inflammatory cytokines, whereas increases expression of MMPs. There were 23 miRNAs, 307 lncRNAs, and 367 mRNAs differentially expressed between Exo and control groups. Exosomes derived from BMSCs may protect trabecular meshwork cells from oxidative stress. Candidate genes responsible for beneficial effects, such as DIO2 and HMOX1, were predicted.

scholarly journals Sodium–glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in rats after cardiac arrest

2021 ◽  
Author(s):  
Yunke Tan ◽  
Kai Yu ◽  
Lian Liang ◽  
Yuanshan Liu ◽  
Fengqing Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Arrest ◽  
Cardiac Function ◽  
Structural Integrity ◽  
Troponin I ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Mitochondrial Activity ◽  
Myocardial Oxidative Stress ◽  
Sglt2 Inhibition

Abstract Background: Sodium–glucose co-transporter 2 (SGLT2) inhibition reduces hyperglycaemia and has beneficial effects in heart failure. However, the effect of SGLT2 inhibition with empagliflozin on acute myocardial dysfunction after cardiac arrest (CA) remains unknown.Methods: Non-diabetic male Sprague–Dawley rats underwent ventricular fibrillation to induce CA, or sham surgery. Rats received 10 mg/kg of empagliflozin or vehicle at 10 minutes after return of spontaneous circulation by intraperitoneal injection. Cardiac function was assessed by echocardiography, histological analysis, molecular markers of myocardial injury, oxidative stress, mitochondrial ultrastructural integrity and metabolism. Results: Empagliflozin did not influence heart rate and blood pressure, but left ventricular function and survival time were significantly higher in the empagliflozin treated group compared to the group treated with vehicle. Empagliflozin also reduced myocardial contraction band necrosis, myocardial fibrosis, serum cardiac troponin I levels and myocardial oxidative stress after CA. Moreover, empagliflozin maintained the structural integrity of myocardial mitochondria and increased mitochondrial activity after CA. In addition, empagliflozin increased circulating and myocardial ketone levels as well as myocardial expression of the 𝛽-hydroxy butyrate dehydrogenase 1. Together these metabolic changes were associated with an increase in cardiac ATP production.Conclusions: Empagliflozin favorably affects cardiac function in non-diabetic rats with acute myocardial dysfunction after CA, associated with reducing glucose levels and increasing ketone body oxidized metabolism. Our data suggest that empagliflozin might be of benefit in patients with acute myocardial dysfunction after CA.

scholarly journals EPA Is Cardioprotective in Male Rats Subjected to Sepsis, but ALA is Not Beneficial

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 371
Author(s):  
Thibault Leger ◽  
Chrystèle Jouve ◽  
Isabelle Hininger-Favier ◽  
Jean-Paul Rigaudiere ◽  
Frédéric Capel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Cecal Ligation ◽  
Female Rats ◽  
Male Rats ◽  
Mechanical Activity ◽  
Coronary Perfusion

It has been proven that dietary eicosapentaenoic acid (C20:5 n-3 or EPA) protects the heart against the deleterious effects of sepsis in female rats. We do not know if this is the case for male rodents. In this case, the efficiency of other n-3 polyunsaturated fatty acids (PUFAs) remains to be determined in both female and male rats. This study aimed at (i) determining whether dietary EPA is cardioprotective in septic male rats; (ii) evaluating the influence of dietary α-linolenic (C18:3 n-3 or ALA) on cardiac function during this pathology; and (iii) finding out the physiological and molecular mechanisms responsible for the observed effects. Sixty male rats were divided into three dietary groups. The animals were fed a diet deficient in n-3 PUFAs (DEF group), a diet enriched with ALA (ALA group) or a diet fortified with EPA (EPA group) for 6 weeks. Thereafter, each group was subdivided into 2 subgroups, one being subjected to cecal ligation and puncture (CLP) and the other undergoing a fictive surgery. Cardiac function was determined in vivo and ex vivo. Several parameters related to the inflammation process and oxidative stress were determined. Finally, the fatty acid compositions of circulating lipids and cardiac phospholipids were evaluated. The results of the ex vivo situation indicated that sepsis triggered cardiac damage in the DEF group. Conversely, the ex vivo data indicated that dietary ALA and EPA were cardioprotective by resolving the inflammation process and decreasing the oxidative stress. However, the measurements of the cardiac function in the in vivo situation modulated these conclusions. Indeed, in the in vivo situation, sepsis deteriorated cardiac mechanical activity in the ALA group. This was suspected to be due to a restricted coronary flow which was related to a lack of cyclooxygenase substrates in membrane phospholipids. Finally, only EPA proved to be beneficial in sepsis. Its action necessitates both resolution of inflammation and increased coronary perfusion. In that sense, dietary ALA, which does not allow the accumulation of vasodilator precursors in membrane lipids, cannot be protective during the pathology.

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