scholarly journals Potential Interaction of Fresh Garlic with Metformin during Ischemia-Reperfusion Induced Cardiac Injury in Diabetic Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Syed Mohammed Basheeruddin Asdaq ◽  
S. Lokaraja ◽  
Abdulhakeem S. Alamri ◽  
Walaa F. Alsanie ◽  
Majid Alhomrani ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Combined Therapy ◽  
Diabetic Rats ◽  
Isolated Rat Heart ◽  
Cardiac Biomarkers ◽  
Tissue Homogenate ◽  
Sprague Dawley ◽  
Creatine Kinase Mb

Background and objectives. Diabetes mellitus is a metabolic illness related to numerous organ damage, dysfunctions, and renal malfunction. In diabetes, oxidative stress plays a crucial part in the biochemical and pathological alterations linked to myocardial ischemia-reperfusion injury (IRI). In this study, an effort was made to evaluate the possible interaction of garlic (Allium sativum) (250 mg/kg) with the biguanide derivative, metformin (MET) (70 mg/kg), on IRI induced myocardial dysfunction in the isolated rat heart. Methods. The study was undertaken on both normoglycemic and alloxan (90 mg/kg) induced diabetic Sprague Dawley rats weighing 150–250 g. At the completion of the treatment phase (30 days for garlic, 250 mg/kg, oral; 10 days for MET, 70 mg/kg, oral), rats were anesthetized and mounted on the modified Langendorff’s apparatus. IRI was produced by myocardial no-flow global ischemia. Developed tension (DT) and heart rate (HR) were recorded both before and after ischemia. The perfusate was collected to estimate the leakage of cardiac biomarkers (Creatine Kinase-MB: CK-MB and Lactate dehydrogenase: LDH). Hearts were removed from the setup and utilized to prepare heart tissue homogenate (HTH) and histological slides. The endogenous antioxidants, superoxide dismutase (SOD) and catalase (CAT), in addition to oxidative thiobarbituric acid substances (TBS), were estimated in HTH. Results. The hemodynamic parameters, including percentage recovery in HR and DT, were found significantly higher in animals pretreated with garlic and MET in diabetic rats (DR). Both SOD and CAT enzyme activities increased significantly while TBS levels were reduced in the HTH of animals treated with garlic and MET. The cardiac markers CK-MB and LDH levels also increased in HTH with a corresponding decrease in the perfusate. The histopathological changes in the heart and pancreas demonstrated noticeable protection of the tissues due to pretreatment with garlic and MET. Taken together, these findings advocate that reactive oxygen species derived from hyperglycemia execute an important function in myocardial global IRI; the therapy of garlic homogenate was found to be effective in alleviating these toxic effects. Conclusion. The combined therapy of MET and garlic provided synergistic cardioprotection, implying that garlic seems to possess promise in lowering toxic parameters by protecting diabetic induced myocardial injury.

scholarly journals Inhibiting mTOR enhanced Cardiac STAT3 Phosphorylation at Site Ser 727 and Attenuated Myocardial Ischemia Reperfusion Injury in Diabetic Rats

2021 ◽  
Author(s):  
Xiang Xie ◽  
Zhongbao Zhao ◽  
Danyong Liu ◽  
Dengwen Zhang ◽  
Yi He ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Mtor Inhibitor ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
H9c2 Cells ◽  
Sprague Dawley ◽  
Mtor Inhibition ◽  
Stat3 Phosphorylation

Abstract Background Reduced levels of myocardial STAT3 activity in diabetic hearts may contribute to the increased susceptibility to ischemia-reperfusion injury (I/RI). The protein mammalian target of rapamycin (mTOR) can regulate metabolism and cell processes and plays major roles in the dynamics of I/RI. However, the role of mTOR in regulation of myocardial STAT3 and thereby affect myocardial I/RI in diabetes at relatively late stages of the disease is unknown. Methods Diabetes was induced by Streptozotocin in Sprague-Dawley rats. Myocardial I/RI was achieved with coronary occlusion for 30 minutes and reperfusion for 2 hours in absence or presence of the mTOR inhibitor rapamycin. In vitro cardiomyocyte hypoxia/re-oxygenation (H/R) was established within H9C2 cells. Results In diabetic rats, the levels of troponin-I (Tn-I), lipid peroxidation products 15-F2t-Isoprostane (15-F2t-Iso) and MDA, and the expression of protein mTOR were all significantly increased,and SOD releasing, the expression of protein phosphorylation of STAT3(p-STAT3-Ser727) were both significantly decreased compared to non-diabetic rats. Myocardial I/RI significantly increased the infract size (IS) and further increased the mTOR activation and decreased p-STAT3-Ser727 compared to diabetic rats. The selective mTOR inhibitor rapamycin reversed these changes and conferred cardioprotective effect. In H9C2 cells, high glucose (HG) significantly increased lactic dehydrogenase (LDH) release, apoptosis cells, ROS release, activation of mTOR, and decreased p-STAT3-Ser727. H/R further increased cellular injury, mTOR knock-down significantly reduced H/R injury. Conclusion Myocardial mTOR was enhanced in diabetes and contributed to I/RI. mTOR inhibition attenuated myocardial I/RI through increasing p-STAT3-Ser727.

Abstract 10773: Curcumin Improves the Outcomes of Cardiopulmonary Resuscitation in a Rat Model of Cardiac Arrest

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Zhengfei Yang ◽  
Jiangang Wang ◽  
Lu Yin ◽  
Shen Zhao ◽  
Ziren Tang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Placebo Group ◽  
Rat Model ◽  
Myocardial Function ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Sprague Dawley ◽  
Successful Resuscitation ◽  
Pre Treatment

Introduction: Curcumin has been proven to provide potent protection of vital organs against regional ischemia reperfusion injury. In this study, we investigated the effects of curcumin on the outcomes of CPR in a rat model of cardiac arrest. Hypothesis: Curcumin reduces the severity of post-CPR myocardial dysfunction and prolong the duration of survival. Method: Sixteen male Sprague-Dawley rats weighing between 450-550g were randomized into two groups: 1) Placebo; 2) Curcumin (100 mg/kg) pre-treatment. Ventricular fibrillation (VF) was induced. After 8 mins of VF, CPR was initiated for 8 mins and defibrillation was then attempted. Myocardial function was measured by echocardiography at baseline and hourly for 4 hours following successful resuscitation. The duration of survival was observed for total 72 hours. Result: Six animals in the placebo group and seven in the curcumin group were successfully resuscitated. Post-resuscitation myocardial function was significantly impaired in all animals. However, myocardial function gradually improved 4 hours after resuscitation and was significantly better in the animals pre-treated with curcumin (Figure). Significantly shorter duration of survival of 40±29 hours was observed in the placebo group. Conclusion: In a rat model of cardiac arrest, curcuminim proves post-resuscitation myocardial dysfunction and prolongs the duration of survival.

scholarly journals Luteolin Attenuates Cardiac Ischemia/Reperfusion Injury in Diabetic Rats by Modulating Nrf2 Antioxidative Function

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Chi Xiao ◽  
Man-Li Xia ◽  
Jue Wang ◽  
Xin-Ru Zhou ◽  
Yang-Yun Lou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Isolated Rat Heart ◽  
Diabetic Heart ◽  
Diabetic Rat ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nrf2 Signaling Pathway

Luteolin has been reported to attenuate ischemia/reperfusion (I/R) injury in the diabetic heart through endothelial nitric oxide synthase- (eNOS-) related antioxidative response. Though the nuclear factor erythroid 2-related factor 2 (Nrf2) is regarded as a key endogenous factor to reduce diabetic oxidative stress, whether luteolin reduces cardiac I/R injury in the diabetic heart via enhancing Nrf2 function needs to be clarified. We hypothesized that pretreatment with luteolin could alleviate cardiac I/R injury in the diabetic heart by affecting the eNOS/Nrf2 signaling pathway. The diabetic rat was produced by a single injection of streptozotocin (65 mg/kg, i.p.) for 6 weeks, and then, luteolin (100 mg/kg/day, i.g.), eNOS inhibitor L-NAME, or Nrf2 inhibitor brusatol was administered for the succedent 2 weeks. After that, the isolated rat heart was exposed to 30 min of global ischemia and 120 min of reperfusion to establish I/R injury. Luteolin markedly ameliorated cardiac function and myocardial viability; upregulated expressions of heme oxygenase-1, superoxide dismutase, glutathione peroxidase, and catalase; and reduced myocardial lactate dehydrogenase release, malondialdehyde, and 8-hydroxydeoxyguanosine in the diabetic I/R heart. All these ameliorating effects of luteolin were significantly reversed by L-NAME or brusatol. Luteolin also markedly reduced S-nitrosylation of Kelch-like ECH-associated protein 1 (Keap1) and upregulated Nrf2 and its transcriptional activity. This effect of luteolin on Keap1/Nrf2 signaling was attenuated by L-NAME. These data reveal that luteolin protects the diabetic heart against I/R injury by enhancing eNOS-mediated S-nitrosylation of Keap1, with subsequent upregulation of Nrf2 and the Nrf2-related antioxidative signaling pathway.

scholarly journals Cardioprotective Effects of Astragalin against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Daoxu Qu ◽  
Jichun Han ◽  
Huanhuan Ren ◽  
Wenxiao Yang ◽  
Xinjie Zhang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Rat Heart ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Isolated Rat Heart ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion ◽  
Isolated Rat

This study aims to evaluate the cardioprotective effects of astragalin against myocardial ischemia/reperfusion (I/R) injury in isolated rat heart. The cardioprotective effects of astragalin on myocardial I/R injury were investigated on Langendorff apparatus. Adult male Sprague-Dawley rats were randomly divided into five groups. The results showed that astragalin pretreatment improved myocardial function. Compared with I/R group, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in coronary flow decreased in astragalin pretreatment groups, whereas superoxide dismutase (SOD) activity and glutathione/glutathione disulfide (GSH/GSSG) ratio significantly increased. The levels of malondialdehyde (MDA), intracellular reactive oxygen species (ROS), tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6) decreased in astragalin-treated groups. The infarct size (IS) and apoptosis rate in hearts from astragalin-treated groups were lower than those in hearts from the I/R group. Western blot analysis also revealed that astragalin preconditioning significantly reduced Bax level, whereas Bcl-2 was increased in the myocardium. Therefore, astragalin exhibited cardioprotective effects via its antioxidative, antiapoptotic, and anti-inflammatory activities.

scholarly journals New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1552-1563
Author(s):  
Rong-Hui Tu ◽  
Dong-Xiao Wang ◽  
Guo-Qiang Zhong ◽  
Jian-Jun Meng ◽  
Hong Wen ◽  
...  
Keyword(s):  
Infarct Size ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Hsp90 Inhibitor ◽  
Myocardial Inflammation ◽  
Sprague Dawley ◽  
Akt Inhibitor ◽  
Creatine Kinase Mb

Abstract Background Activation of the complement component 5a (C5a) and nuclear factor κB (NF-κB) signaling is an important feature of myocardial ischemia/reperfusion (I/R) injury and recent studies show that morphine postconditioning (MP) attenuates the myocardial injury. However, the mediating cardioprotective mechanisms remain unclear. The present study explores the role and interaction of heat shock protein 90 (HSP90), Akt, C5a, and NF-κB in MP-induced cardioprotection. Methods Male Sprague Dawley rats (n = 160) were randomized into eight groups (n = 20 per group). Rats in the sham group underwent thoracotomy, passing the ligature through the heart but without tying it (150 min), and the other seven groups were subjected to 30 min of anterior descending coronary artery occlusion followed by 2 h of reperfusion and the following treatments: I/R (30 min of ischemia and followed by 2 h of reperfusion); ischemic postconditioning (IPostC, 30 s of ischemia altered with 30 s of reperfusion, repeated for three cycles, and followed by reperfusion for 2 h); MP (0.3 mg/kg morphine administration 10 min before reperfusion); MP combined with the HSP90 inhibitor geldanamycin (GA, 1 mg/kg); MP combined with the Akt inhibitor GSK-690693 (GSK, 20 mg/kg); and MP combined with the C5a inhibitor PMX205 (PMX, 1 mg/kg/day, administration via drinking water for 28 days) and MP combined with the NF-κB inhibitor EVP4593 (QNZ, 1 mg/kg). All inhibitors were administered 10 min before morphine and followed by 2 h reperfusion. Results MP significantly reduced the I/R-induced infarct size, the apoptosis, and the release of cardiac troponin I, lactate dehydrogenase (LDH), and creatine kinase-MB. These beneficial effects were accompanied by increased expression of HSP90 and p-Akt, and decreased expression of C5a, NF-κB, tumor necrosis factor α, interleukin-1β, and intercellular cell adhesion molecule 1. However, HSP90 inhibitor GA or Akt inhibitor GSK increased the expression of C5a and NF-κB and prevented MP-induced cardioprotection. Furthermore, GA inhibited the MP-induced upregulation of p-Akt, while GSK did not affect HSP90, indicating that p-Akt acts downstream of HSP90 in MP-induced cardioprotection. In addition, C5a inhibitor PMX enhanced the MP-induced downregulation of NF-κB, while NF-κB inhibitor QNZ had no effect on C5a, indicating that the C5a/NF-κB signaling pathway is involved in MP-induced cardioprotection. Conclusion HSP90 is critical for MP-mediated cardioprotection possibly by promoting the phosphorylation of Akt and inhibiting the activation of C5a and NF-κB signaling and the subsequent myocardial inflammation, ultimately attenuating the infarct size and cardiomyocyte apoptosis.

Abstract 298: Identification of LncRNA-miRNA-mRNA Network in Myocardium After Successful Resuscitation in a Rat Model of Prolonged Cardiac Arrest

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Jingying Hou ◽  
Zhengfei Yang ◽  
Wanchun Tang
Keyword(s):  
Cardiac Arrest ◽  
Rat Model ◽  
Regulatory Network ◽  
High Throughput Sequencing ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Expression Profiles ◽  
Ischemia Reperfusion ◽  
Sprague Dawley ◽  
Successful Resuscitation

Introduction: Previous studies have indicated that lncRNA participates in regional myocardial ischemia-reperfusion injury (IRI). However, the lncRNA-miRNA-mRNA crosstalk in the global myocardial IRI, which is implicated in the pathophysiology of post-resuscitation myocardial dysfunction (PRMD), has still not been explored. Hypothesis: To identify lncRNA-miRNA-mRNA regulatory network in myocardium after successful resuscitation in a rat model of prolonged cardiac arrest. Methods: Six male Sprague Dawley rats were randomized into sham control and ventricular fibrillation (VF)-CPR groups, with three rats in each group. VF was induced and untreated for 8 minutes. Defibrillation was attempted after 8 minutes of CPR. Heart tissue was obtained at 6 hours after resuscitation and lncRNA, miRNA and mRNA expression profiles were examined by using high-throughput sequencing. LncRNA-miRNA-mRNA interaction network was predicted and constructed. Results: Numbers of differentially expressed (DE) lncRNA, miRNA and mRNA were detected (Fig 1A). LncRNAs co-located or co-expressed target mRNAs and DE mRNAs were revealed (Fig 1B). The intersection of DE mRNAs with targeted mRNA of DE miRNAs was made (Fig 1C). A total of 129 feed forward loops were predicted as lncRNA-associated ceRNA networks,with 126 lncRNA (up)-miRNA (down)-mRNA (up) and 3 lncRNA (down)-miRNA (up)-mRNA (down) (Fig 2). Conclusions: LncRNA-miRNA-mRNAs network was predicted and constructed in myocardium after successful resuscitation in a rat model of prolonged cardiac arrest. Further exploration into the specific functional roles of the ceRNA regulatory network will be conducive for the treatment of PRMD.

scholarly journals Punicalagin Pretreatment Attenuates Myocardial Ischemia-Reperfusion Injury via Activation of AMPK

2017 ◽  
Vol 45 (01) ◽  
pp. 53-66 ◽  
Author(s):  
Mingge Ding ◽  
Yin Wang ◽  
Di Sun ◽  
Zhenhua Liu ◽  
Jie Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Adenosine Monophosphate ◽  
Pomegranate Juice ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Compound C ◽  
Myocardial Oxidative Stress ◽  
Creatine Kinase Mb

Punicalagin (PUN), a major bioactive component in pomegranate juice, has been proven to exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) insult via anti-oxidant properties. This study aims to investigate whether PUN provides cardioprotection against myocardial I/R (MI/R) injury and the underlying mechanisms. PUN (30[Formula: see text]mg/kg/d) or vehicle was intragastrically administered to Sprague-Dawley rats for one week before the operation. MI/R was induced by ligating the left anterior descending coronary artery for 30[Formula: see text]min and subsequent reperfusion for 3[Formula: see text]h. PUN pretreatment conferred cardioprotective effects against MI/R injury by improving cardiac function, limiting infarct size, reducing serum creatine kinase-MB and lactate dehydrogenase activities, and suppressing cardiomyocyte apoptosis. Moreover, PUN pretreatment inhibited I/R-induced myocardial oxidative stress as evidenced by decreased generation of superoxide content and malonaldialdehyde formation and increased antioxidant capability. Furthermore, PUN pretreatment increased adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation in I/R hearts. AMPK inhibitor compound c inhibited PUN-enhanced AMPK phosphorylation, and blunted PUN-mediated anti-oxidative effects and cardioprotection. These results indicate for the first time that PUN pretreatment protect against I/R-induced oxidative stress and myocardial injury via activation of AMPK.

scholarly journals Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kei Hayashida ◽  
Ryosuke Takegawa ◽  
Muhammad Shoaib ◽  
Tomoaki Aoki ◽  
Rishabh C. Choudhary ◽  
...  
Keyword(s):  
Systematic Review ◽  
Reperfusion Injury ◽  
Animal Studies ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Human Studies ◽  
Cochrane Library

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.

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