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.

Calorie restriction attenuates inflammatory responses to myocardial ischemia-reperfusion injury

2001 ◽  
Vol 280 (5) ◽  
pp. H2094-H2102 ◽  
Author(s):  
B. Chandrasekar ◽  
J. F. Nelson ◽  
J. T. Colston ◽  
G. L. Freeman
Keyword(s):  
Oxidative Stress ◽  
Dna Binding ◽  
Antioxidant Enzyme ◽  
Calorie Restriction ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Myocardial Oxidative Stress

The life-prolonging effects of calorie restriction (CR) may be due to reduced damage from cumulative oxidative stress. Our goal was to determine the long-term effects of moderate dietary CR on the myocardial response to reperfusion after a single episode of sublethal ischemia. Male Fisher 344 rats were fed either an ad libitum (AL) or CR (40% less calories) diet. At age 12 mo the animals were anaesthetized and subjected to thoracotomy and a 15-min left-anterior descending coronary artery occlusion. The hearts were reperfused for various periods. GSH and GSSG levels, nuclear factor-κB (NF-κB) DNA binding activity, cytokine, and antioxidant enzyme expression were assessed in the ischemic zones. Sham-operated animals served as controls. Compared with the AL diet, chronic CR limited oxidative stress as seen by rapid recovery in GSH levels in previously ischemic myocardium. CR reduced DNA binding activity of NF-κB. The κB-responsive cytokines interleukin-1β and tumor necrosis factor-α were transiently expressed in the CR group but persisted longer in the AL group. Furthermore, expression of manganese superoxide dismutase, a key antioxidant enzyme, was significantly delayed in the AL group. Collectively these data indicate that CR significantly attenuates myocardial oxidative stress and the postischemic inflammatory response.

Neuroprotective Effects of Bone Marrow Mononuclear Cells Therapy in a Rat Model of Ischemia Stroke

2020 ◽  
Vol 10 (3) ◽  
pp. 346-351
Author(s):  
Jianfeng Liu ◽  
Yamei Hu ◽  
Gang Li ◽  
Qianlin Zhang ◽  
Jiewen Zhang
Keyword(s):  
Bone Marrow ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Bone Marrow Mononuclear Cells ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Rat Models

Objective: Bone marrow mononuclear cells (BMMCs) are considered a potential approach to promote the recovery of stroke-induced neurological deficit. However, the exact mechanism of BMMCs in nerve function recovery is still unclear. Methods: Adult Sprague-Dawley (SD) rat models of cerebral ischemia-reperfusion injury was established by using thread method. BMMCs were transplanted into rat models. Neurological deficits were evaluated by Longa score scale. Immunohistochemistry assay were employed to examine the expression of GFAP and Nogo-A around the ischemic foci in the right frontal lobe. Caspase-3 activity was examined by Western Blot. Results: Rats in BMMCs group had lessened neurological deficits and cleaved Caspase-3 expression on day 21 after reper-fusion, as well as higher expression of GFAP [(37.62±2.45) vs. (27.62±1.69) and (38.00±1.85) vs. (27.25±1.83), P < 0.05] and lower expression of Nogo-A [(28.88±2.64) vs. (32.50±1.60) and (23.87±2.36) vs. (32.00±1.85), P < 0.05] on day 14 and 21 after reperfusion. Meanwhile, the expression of Nogo-A on day 21 was lower than that on day 14 after reperfusion [(23.87±2.36) vs. (28.88±2.64), P < 0.05] in BMMCs group. Conclusion: These findings suggested that BMMCs treatment could improve the functional recovery of neurological deficits in rats with MCAO, which was probably related to enhanced expression of GFAP and reduced Nogo-A expression and Caspase-3 activity in the ischemic brain tissues.

scholarly journals Therapeutic Potential of Novel Twin Compounds Containing Tetramethylpyrazine and Carnitine Substructures in Experimental Ischemic Stroke

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Ziying Wang ◽  
Zhuanli Zhou ◽  
Xinbing Wei ◽  
Mingwei Wang ◽  
Bi-Ou Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
The Novel ◽  
Neuroprotective Effects ◽  
Chemical Structures ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Blood Brain Barrier Integrity

Although studies have seen dramatic advances in the understanding of the pathogenesis of stroke such as oxidative stress, inflammation, excitotoxicity, calcium overload and apoptosis, the delivery of stroke therapies is still a great challenge. In this study, we designed and synthesized a series of novel twin compounds containing tetramethylpyrazine and carnitine substructures and explored their therapeutic potential and mechanism in stroke-related neuronal injury. We first screened the neuroprotective effects of candidate compounds and found that among the tested compounds, LR134 and LR143 exhibited significant neuroprotection as evidenced by reducing cerebral infarct and edema, improving neurological function as well as blood-brain barrier integrity in rats after cerebral ischemia/reperfusion injury. We further demonstrated that the neuroprotective effects of compounds LR134 and LR143 were associated with the reduced inflammatory responses and NADPH oxidase- (NOX2-) mediated oxidative stress and the protection of mitochondria accompanied by the improvement of energy supply. In summary, this study provides direct evidence showing that the novel twin compounds containing tetramethylpyrazine and carnitine substructures have neuroprotective effects with multiple therapeutic targets, suggesting that modulation of these chemical structures may be an innovative therapeutic strategy for treating patients with stroke.

Abstract 032: Impaired Cardiac Autophagy In Metabolic Syndrome Despite Intact AMPK And mTOR Signaling

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Nandini Ravindran ◽  
Carlos Bazan ◽  
Bruce R Ito ◽  
Roberta A Gottlieb ◽  
Robert M Mentzer
Keyword(s):  
Metabolic Syndrome ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mammalian Target Of Rapamycin ◽  
Adenosine Monophosphate ◽  
Sprague Dawley ◽  
Downstream Target ◽  
Extracellular Milieu ◽  
Adult Rat ◽  
Underlying Mechanisms

Objective: We previously reported that basal cardiac autophagy is lower in the setting of metabolic syndrome (MetS) (obesity, dyslipidemia, insulin resistance) and is associated with attenuation of cardioprotection after ischemic preconditioning. To understand the underlying mechanisms and exclude effects of the extracellular milieu, we investigated the roles of two major cellular energy sensing pathways, adenosine monophosphate-activated protein kinase (AMPK), and mammalian target of rapamycin (mTOR), using adult rat ventricular cardiomyocytes (ARVM) isolated from Sprague Dawley (SD) and Zucker obese (ZO) rats. Methods: ARVM were cultured overnight and subjected to nutrient deprivation (1 hr), or treated with 1µM phenformin (Ph), an AMPK activator, or 5µM rapamycin (Rap), an mTOR inhibitor. Immunoblotting was used to measure phosphorylation of AMPK, p70S6 kinase (a downstream target of mTOR), LC3-I, -II, and p62 (autophagic clearance). Results: In ARVM from SD rats, starvation or Ph increased p-AMPK and decreased p-p70S6K, accompanied by increased LC3-II and 50% reduction in p62. Rapamycin decreased phosphorylation of p70S6K, increased LC3-II and decreased p62. In ZO ARVM, Ph and Rap also activated AMPK and inhibited mTOR; however, LC3-II was unchanged (Fig.) and p62 clearance was blunted. Conclusions: Despite appropriate activation of AMPK and inhibition of mTOR, autophagy is impaired in ARVM from ZO rats. These cells retain the MetS phenotype, facilitating efforts to delineate the molecular basis of impaired autophagy and vulnerability to ischemia/reperfusion injury in MetS. This could lead to new approaches to myocardial protection in at-risk patients.

scholarly journals MicroRNA-223-3p Protect Against Radiation-Induced Cardiac Toxicity by Alleviating Myocardial Oxidative Stress and Programmed Cell Death via Targeting the AMPK Pathway

2022 ◽  
Vol 9 ◽  
Author(s):  
Dao-ming Zhang ◽  
Jun-jian Deng ◽  
Yao-gui Wu ◽  
Tian Tang ◽  
Lin Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Myocardial Injury ◽  
Adenosine Monophosphate ◽  
Dependent Manner ◽  
Protective Effects ◽  
Compound C ◽  
Myocardial Oxidative Stress ◽  
Radiation Induced

Objectives: Radiotherapy improves the survival rate of cancer patients, yet it also involves some inevitable complications. Radiation-induced heart disease (RIHD) is one of the most serious complications, especially the radiotherapy of thoracic tumors, which is characterized by cardiac oxidative stress disorder and programmed cell death. At present, there is no effective treatment strategy for RIHD; in addition, it cannot be reversed when it progresses. This study aims to explore the role and potential mechanism of microRNA-223-3p (miR-223-3p) in RIHD.Methods: Mice were injected with miR-223-3p mimic, inhibitor, or their respective controls in the tail vein and received a single dose of 20 Gy whole-heart irradiation (WHI) for 16 weeks after 3 days to construct a RIHD mouse model. To inhibit adenosine monophosphate activated protein kinase (AMPK) or phosphodiesterase 4D (PDE4D), compound C (CompC) and AAV9-shPDE4D were used.Results: WHI treatment significantly inhibited the expression of miR-223-3p in the hearts; furthermore, the levels of miR-223-3p decreased in a radiation time-dependent manner. miR-223-3p mimic significantly relieved, while miR-223-3p inhibitor aggravated apoptosis, oxidative damage, and cardiac dysfunction in RIHD mice. In addition, we found that miR-223-3p mimic improves WHI-induced myocardial injury by activating AMPK and that the inhibition of AMPK by CompC completely blocks these protective effects of miR-223-3p mimic. Further studies found that miR-223-3p lowers the protein levels of PDE4D and inhibiting PDE4D by AAV9-shPDE4D blocks the WHI-induced myocardial injury mediated by miR-223-3p inhibitor.Conclusion: miR-223-3p ameliorates WHI-induced RIHD through anti-oxidant and anti-programmed cell death mechanisms via activating AMPK by PDE4D regulation. miR-223-3p mimic exhibits potential value in the treatment of RIHD.

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 Effects of Alpha-Mangostin Encapsulated in Nanostructured Lipid Carriers in Mice with Cerebral Ischemia Reperfusion Injury

2021 ◽  
Vol 50 (7) ◽  
pp. 2007-2015
Author(s):  
Romgase Sakamula ◽  
Teerapong Yata ◽  
Wachiryah Thong-asa
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nanostructured Lipid Carriers ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Cerebral ischemia reperfusion injury (CIRI) is a phenomenon in which the cerebral blood supply is restored after a period of ischemia, resulting in irreversible damage to brain tissue. Oxidative stress plays a crucial role in the development of CIRI, therefore, targeting oxidative stress might be an effective strategy for CIRI prevention and treatment. Many therapeutic substances possess antioxidant and protective properties against neurodegenerative disorders but lack of in vivo application due to their solubility, and bioavailability. We investigated the effects of alpha-mangostin (αM) encapsulated in nanostructured lipid carriers (αM-NLC) on CIRI in mice. Forty male ICR mice were randomly divided into four groups: Sham, ischemia reperfusion (IR), ischemia reperfusion with 25 mg/kg of αM (IR+αM), and ischemia reperfusion with 25 mg/kg of αM-NLC (IR+αM-NLC). After 6 days of oral administrations, IR was delivered using 30 min of bilateral common carotid artery occlusion, followed by 45 min of reperfusion. Cerebral infarction volume, hippocampal neuronal and corpus callosum (CC) white matter damage, malondialdehyde (MDA) level, and catalase (CAT) activity were evaluated. Our results indicated that αM and αM-NLC prevent lipid peroxidation as well as hippocampal CA1, CA3, and CC damage (p<0.05). Only αM-NLC prevented cerebral infarction and enhanced CAT activity (p<0.05). We therefore conclude that αM and αM-NLC have neuroprotective effects against CIRI, and NLC increases therapeutic efficacy of αM against CIRI.

Detrimental role of homocysteine in renal ischemia-reperfusion injury

2007 ◽  
Vol 292 (5) ◽  
pp. F1354-F1363 ◽  
Author(s):  
Gamika A. Prathapasinghe ◽  
Yaw L. Siow ◽  
Karmin O
Keyword(s):  
Oxidative Stress ◽  
Renal Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Kidney ◽  
Sprague Dawley ◽  
Functional Benefit ◽  
Key Enzyme ◽  
Reduced Activity

Ischemia followed by reperfusion is a major cause for renal injury in both native kidney and renal allografts. Hyperhomocysteinemia, a condition of elevated plasma homocysteine (Hcy) level, is associated with cardiovascular diseases. Recent evidence suggests that Hcy, at higher levels, may be harmful to other organs such as the kidney. In this study, we investigated the role of Hcy in ischemia-reperfusion-induced renal injury. The left kidney of a Sprague-Dawley rat was subjected to either 30-min or 1-h ischemia followed by 1- or 24-h reperfusion. Ischemia-reperfusion caused a significant increase in peroxynitrite formation and lipid peroxidation in kidneys, which reflected oxidative stress. The number of apoptotic cells in those kidneys was also markedly increased. Hcy levels were elevated 2.9- and 1.5-fold in kidneys subjected to ischemia alone or ischemia-reperfusion, respectively. Further investigation revealed that elevation of Hcy level in the kidney upon ischemia-reperfusion was due to reduced activity of cystathionine-β-synthase, a key enzyme in Hcy metabolism. Administration of anti-Hcy antibodies into the kidney not only abolished ischemia-reperfusion-induced oxidative stress and cell death in the kidneys but also restored renal function after 1 h of reperfusion. However, such a protective effect was not sustained after 24 h of reperfusion. In conclusion, ischemia-reperfusion impairs Hcy metabolism in the kidney. Hcy, at elevated levels, is capable of inducing oxidative stress and renal injury. Neutralization of Hcy with antibodies offers transient functional benefit against ischemia-reperfusion-induced oxidative stress and renal injury. These results suggest that Hcy may play a detrimental role in the kidney during ischemia-reperfusion.

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