scholarly journals ILEX PARAGUARIENSIS, EXERCISE AND CARDIOPROTECTION: A retrospective analysis

2018 ◽  
Author(s):  
Fábio Cahuê ◽  
José Hamilton Matheus Nascimento ◽  
Luciane Barcellos ◽  
Veronica P. Salerno
Keyword(s):  
Data Science ◽  
Molecular Mechanisms ◽  
Cardiac Tissue ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Ilex Paraguariensis ◽  
Ros Generation ◽  
Yerba Mate ◽  
Reductive Stress ◽  
Apparent Loss

AbstractStudies on strategies to generate cardioprotective effects have been on the rise. Previous work by our group with an ex vivo model of ischemia/reperfusion has shown that both the short-term consumption of yerba mate and exercise can each induce protection of cardiac function independently. Surprising, the two strategies together do not, with an apparent loss of their respective cardioprotection activity. To improve our understanding of the mechanisms involved without reperforming the experiments, we have conducted a retrospective data science-analysis that have produced new insights. The analysis shows that yerba mate generated reductive stress. Alone, this stress increased redox damage in the heart that appears to have led to a protective conditioning. In combination with exercise, the effects of mate inhibited the intermittent ROS generation promoted by exercise alone, which diminished the adaptive response in the heart. These results suggest that an understanding of the molecular mechanisms involved with the yerba mate-promoted reductive stress in cardiac tissue could lead to improved strategies to induce cardioprotection.

scholarly journals Astragaloside IV Attenuates Myocardial Ischemia-Reperfusion Injury from Oxidative Stress by Regulating Succinate, Lysophospholipid Metabolism, and ROS Scavenging System

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Miaomiao Jiang ◽  
Jingyu Ni ◽  
Yuanlin Cao ◽  
Xiaoxue Xing ◽  
Qian Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Ros Scavenging ◽  
Astragaloside Iv ◽  
Wide Range

Astragaloside IV is one of the main active ingredients isolated from Astragalus membranaceus. Here we confirmed its protective effect against cardiac ischemia-reperfusion (I/R) injury and aimed to investigate the potential molecular mechanisms involved. Pretreatment of ex vivo and in vivo I/R-induced rat models by astragaloside IV significantly prevented the ratio of myocardium infarct size, systolic and diastolic dysfunction, and the production of creatine kinase and lactate dehydrogenase. Metabolic analyses showed that I/R injury caused a notable reduction of succinate and elevation of lysophospholipids, indicating excessive reactive oxygen species (ROS) generation driven by succinate’s rapid reoxidization and glycerophospholipid degradation. Molecular validation mechanistically revealed that astragaloside IV stimulated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) released from Kelch-like ECH-associated protein 1 (Keap1) and translocated to the nucleus to combine with musculoaponeurotic fibrosarcoma (Maf) to initiate the transcription of antioxidative gene heme oxygenase-1 (HO-1), which performed a wide range of ROS scavenging processes against pathological oxidative stress in the hearts. As expected, increasing succinate and decreasing lysophospholipid levels were observed in the astragaloside IV-pretreated group compared with the I/R model group. These results suggested that astragaloside IV ameliorated myocardial I/R injury by modulating succinate and lysophospholipid metabolism and scavenging ROS via the Nrf2 signal pathway.

scholarly journals Normothermic Ex-vivo Kidney Perfusion in a Porcine Auto-Transplantation Model Preserves the Expression of Key Mitochondrial Proteins: An Unbiased Proteomics Analysis

2020 ◽  
Author(s):  
Caitriona M. McEvoy ◽  
Sergi Clotet-Freixas ◽  
Tomas Tokar ◽  
Chiara Pastrello ◽  
Shelby Reid ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Kidney Injury ◽  
Tca Cycle ◽  
Proteomics Analysis ◽  
Beneficial Effects ◽  
Kidney Perfusion

AbstractNormothermic ex-vivo kidney perfusion (NEVKP) results in significantly improved graft function in porcine auto-transplant models of DCD injury compared to static cold storage (SCS); however, the molecular mechanisms underlying these beneficial effects remain unclear. We performed an unbiased proteomics analysis of 28 kidney biopsies obtained at 3 time points from pig kidneys subjected to 30-minutes of warm ischemia, followed by 8 hours of NEVKP or SCS, and auto-transplantation. 70/6593 proteins quantified were differentially expressed between NEVKP and SCS groups (FDR<0.05). Proteins increased in NEVKP mediated key metabolic processes including fatty acid ß-oxidation, the TCA-cycle and oxidative phosphorylation. Comparison of our findings with external datasets of ischemia-reperfusion, and other models of kidney injury confirmed that 47 of our proteins represent a common signature of kidney injury reversed or attenuated by NEVKP. We validated key metabolic proteins (ETFB, CPT2) by immunoblotting. Transcription factor databases identified PPARGC1A, PPARA/G/D and RXRA/B as the upstream regulators of our dataset, and we confirmed their increased expression in NEVKP with RT-PCR. The proteome-level changes observed in NEVKP mediate critical metabolic pathways that may explain the improved graft function observed. These effects may be coordinated by PPAR-family transcription factors, and may represent novel therapeutic targets in ischemia-reperfusion injury.

scholarly journals Compound K Inhibits Autophagy-Mediated Apoptosis Through Activation of the PI3K-Akt Signaling Pathway Thus Protecting Against Ischemia/Reperfusion Injury

2018 ◽  
Vol 47 (6) ◽  
pp. 2589-2601 ◽  
Author(s):  
Xiangyan Li ◽  
Qingxia Huang ◽  
Manying Wang ◽  
Xiuci Yan ◽  
Xinying Song ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Mitochondrial Damage ◽  
Tunel Staining ◽  
Ros Generation ◽  
Akt Signaling Pathway ◽  
Compound K

Background/Aims: A series of reports revealed that autophagy and apoptosis exerted detrimental effects on the pathology of cardiac ischemia/reperfusion (I/R) injury. Ginsenoside compound K (CK), a major intestinal metabolite underlying the pharmacological actions of orally administered ginseng, has a protective effect against myocardial I/R injury. However, the molecular mechanisms by which CK protects against I/R injury remain unclear. In this study, we hypothesized that the cardioprotective effects of CK against I/R injury are mediated by inhibiting autophagy/apoptosis-related signaling pathways in H9c2 cardiomyocyte cells. Methods: H9c2 cells were incubated with CK and exposed to I/R. Cell viability and damage was analyzed by MTT and lactate dehydrogenase assays. Reactive oxygen species (ROS) generation, mitochondrial damage, and cell apoptosis were analyzed by flow cytometry and TUNEL staining. The expression of autophagy, apoptosis, and related signaling proteins was analyzed by Western blotting and immunofluorescence staining. Results: CK pretreatment promoted cell viability and attenuated ROS accumulation and intracellular mitochondrial damage induced by I/R injury Moreover, CK reduced autophagy by regulating the formation of phagocytic precursors to autophagosomes and also inhibited apoptosis through a mitochondrial-mediated pathway. Additionally the cardioprotective effect of CK against I/R injury was mainly through the activation of the PI3K-Akt signaling pathway. Conclusions: CK pretreatment inhibits autophagy-mediated apoptosis induced by I/R injury through the activation of the PI3K-Akt signaling pathway, which reveals that CK may be one of the key bioactive ingredients of ginseng for the treatment of myocardial I/R injury.

scholarly journals Ischemia-Reperfusion Injury in Marginal Liver Grafts and the Role of Hypothermic Machine Perfusion: Molecular Mechanisms and Clinical Implications

2020 ◽  
Vol 9 (3) ◽  
pp. 846 ◽  
Author(s):  
Zoltan Czigany ◽  
Isabella Lurje ◽  
Moritz Schmelzle ◽  
Wenzel Schöning ◽  
Robert Öllinger ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Organ Shortage ◽  
Machine Perfusion ◽  
Hypothermic Machine Perfusion ◽  
Critical Organ

Ischemia-reperfusion injury (IRI) constitutes a significant source of morbidity and mortality after orthotopic liver transplantation (OLT). The allograft is metabolically impaired during warm and cold ischemia and is further damaged by a paradox reperfusion injury after revascularization and reoxygenation. Short-term and long-term complications including post-reperfusion syndrome, delayed graft function, and immune activation have been associated with IRI. Due to the current critical organ shortage, extended criteria grafts are increasingly considered for transplantation, however, with an elevated risk to develop significant features of IRI. In recent years, ex vivo machine perfusion (MP) of the donor liver has witnessed significant advancements. Here, we describe the concept of hypothermic (oxygenated) machine perfusion (HMP/HOPE) approaches and highlight which allografts may benefit from this technology. This review also summarizes clinical applications and the main aspects of ongoing randomized controlled trials on hypothermic perfusion. The mechanistic aspects of IRI and hypothermic MP—which include tissue energy replenishment, optimization of mitochondrial function, and the reduction of oxidative and inflammatory damage following reperfusion—will be comprehensively discussed within the context of current preclinical and clinical evidence. Finally, we highlight novel trends and future perspectives in the field of hypothermic MP in the context of recent findings of basic and translational research.

scholarly journals Dietary flaxseed enhances antioxidant defenses and is protective in a mouse model of lung ischemia-reperfusion injury

2008 ◽  
Vol 294 (2) ◽  
pp. L255-L265 ◽  
Author(s):  
James C. Lee ◽  
Faiz Bhora ◽  
Jing Sun ◽  
Guanjun Cheng ◽  
Evguenia Arguiri ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Murine Model ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Lung Damage ◽  
Antioxidant Defenses ◽  
Ros Generation ◽  
Heme Oxygenase 1

Dietary flaxseed (FS) is a nutritional whole grain with high contents of omega-3 fatty acids and lignans with anti-inflammatory and antioxidant properties. We evaluated FS in a murine model of pulmonary ischemia-reperfusion injury (IRI) by dietary supplementation of 0% (control) or 10% (treatment) FS before IRI. Mice fed 0% FS undergoing IRI had a significant decrease in arterial oxygenation (PaO2) and a significant increase in bronchoalveolar lavage (BAL) protein compared with sham-operated mice. However, mice fed 10% FS undergoing IRI had a significant improvement in both PaO2 and BAL protein compared with mice fed 0% FS undergoing IRI. In addition, oxidative lung damage was decreased in 10% FS-supplemented mice undergoing IRI, as assessed by malondialdehyde levels. Immunohistochemical staining of lungs for iPF2α-III F2 isoprostane, a measure of lipid oxidation, was diminished. FS-supplemented mice had less reactive oxygen species (ROS) release from the vascular endothelium in lungs in an ex vivo model of IRI, and alveolar macrophages isolated from FS-fed mice had significantly reduced ROS generation in response to oxidative burst. Pulmonary microvascular endothelial cells produced less ROS in a flow cessation model of ischemia when preincubated with purified FS lignan metabolites. Pharmacological inhibition of heme oxygenase-1 (HO-1) resulted in only a partial reduction of FS protection in the same model. We conclude that dietary FS is protective against IRI in an experimental murine model and that FS affects ROS generation and ROS detoxification via pathways not limited to upregulation of antioxidant enzymes such as HO-1.

Short-term consumption of Ilex paraguariensis extracts protects isolated hearts from ischemia/reperfusion injury and contradicts exercise-mediated cardioprotection

2017 ◽  
Vol 42 (11) ◽  
pp. 1149-1157 ◽  
Author(s):  
Fábio Cahuê ◽  
Simone Souza ◽  
Camilli Fernanda Martins dos Santos ◽  
Victor Machado ◽  
José H.M. Nascimento ◽  
...  
Keyword(s):  
Body Weight ◽  
Ischemia Reperfusion Injury ◽  
Diastolic Pressure ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Maximum Velocity ◽  
Protein Carbonyl ◽  
Ilex Paraguariensis ◽  
Short Term ◽  
Sod Activity

Perfusion of hearts with extracts of Ilex paraguariensis (IP/mate) appears to reduce ischemia/reperfusion (I/R) injury. To determine if oral consumption of IP/mate can provide similar cardioprotection, short-term consumption was investigated alone or in association with exercise in rats. Animals were grouped into control (C), IP/mate consumption (M), exercise (E), and exercise with mate (E+M). M and E+M groups consumed IP/mate (1 g·kg−1 body weight in 1 mL water) by gavage. E and E+M groups swam 7× per week for 30 min carrying an additional 5% of body weight. After 1 week, hearts were tested ex vivo to measure left ventricle developed pressure (LVDP), systolic and end diastolic pressure (LVSP/LVEDP), maximum velocity of contraction and relaxation (dP/dt+ and dP/dt–) during I/R and infarction size. In addition, cardiac tissue was analyzed for oxidative stress by lipid peroxidation and protein carbonyl levels along with activity of catalase and superoxide dismutase (SOD). LVDP was higher in hearts from M and E groups as well as decreased infarction sizes than others. At the end of reperfusion, dP/dt+ was increased in E and M and dP/dt– was higher in M. LVSP was higher in M and E compared with C. Protein carbonyl and thiobarbituric acid reactive substances levels were higher in M while SOD activity was increased in E. No differences were observed in other activities. The results suggest that short-term consumption of IP/mate has protective effects on heart I/R injury similar to exercise, but the combination of these interventions appears to contradict the beneficial adaptations from exercise.

scholarly journals S1P lyase: a novel therapeutic target for ischemia-reperfusion injury of the heart

2011 ◽  
Vol 300 (5) ◽  
pp. H1753-H1761 ◽  
Author(s):  
Padmavathi Bandhuvula ◽  
Norman Honbo ◽  
Guan-Ying Wang ◽  
Zhu-Qiu Jin ◽  
Henrik Fyrst ◽  
...  
Keyword(s):  
Infarct Size ◽  
Cardiac Tissue ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Protein Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Federal Drug Administration ◽  
S1p Lyase

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that promotes cardiomyocyte survival and contributes to ischemic preconditioning. S1P lyase (SPL) is a stress-activated enzyme responsible for irreversible S1P catabolism. We hypothesized that SPL contributes to oxidative stress by depleting S1P pools available for cardioprotective signaling. Accordingly, we evaluated SPL inhibition as a strategy for reducing cardiac ischemia-reperfusion (I/R) injury. We measured SPL expression and enzyme activity in murine hearts. Basal SPL activity was low in wild-type cardiac tissue but was activated in response to 50 min of ischemia ( n = 5, P < 0.01). Hearts of heterozygous SPL knockout mice exhibited reduced SPL activity, elevated S1P levels, smaller infarct size, and increased functional recovery after I/R compared with littermate controls ( n = 5, P < 0.01). The small molecule tetrahydroxybutylimidazole (THI) is a Federal Drug Administration-approved food additive that inhibits SPL. When given overnight at 25 mg/l in drinking water, THI raised S1P levels and reduced SPL activity ( n = 5, P < 0.01). THI reduced infarct size and enhanced hemodynamic recovery in response to 50 min of ischemia and to 40 min of reperfusion in ex vivo hearts ( n = 7, P < .01). These data correlated with an increase in MAP kinase-interacting serine/threonine kinase 1, eukaryotic translation initiation factor 4E, and ribosomal protein S6 phosphorylation levels after I/R, suggesting that SPL inhibition enhances protein translation. Pretreatment with an S1P1 and S1P3 receptor antagonist partially reversed the effects of THI. These results reveal, for the first time, that SPL is an ischemia-induced enzyme that can be targeted as a novel strategy for preventing cardiac I/R injury.

LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

2020 ◽  
Vol 17 (4) ◽  
pp. 394-401
Author(s):  
Yuanhua Wu ◽  
Yuan Huang ◽  
Jing Cai ◽  
Donglan Zhang ◽  
Shixi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cell Activity ◽  
Ht22 Cells ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

scholarly journals The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

2020 ◽  
Vol 31 (4) ◽  
pp. 716-730 ◽  
Author(s):  
Marc Johnsen ◽  
Torsten Kubacki ◽  
Assa Yeroslaviz ◽  
Martin Richard Späth ◽  
Jannis Mörsdorf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Caloric Restriction ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hypoxic Preconditioning ◽  
Preventive Strategies ◽  
Gene Expression Signatures

BackgroundAlthough AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance.MethodsTo identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury.ResultsThe gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI.ConclusionsThis comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

scholarly journals Vitamin D Deficiency Induces Chronic Pain and Microglial Phenotypic Changes in Mice

2021 ◽  
Vol 22 (7) ◽  
pp. 3604
Author(s):  
Nicola Alessio ◽  
Carmela Belardo ◽  
Maria Consiglia Trotta ◽  
Salvatore Paino ◽  
Serena Boccella ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Vitamin D ◽  
Chronic Pain ◽  
Vitamin D Deficiency ◽  
Morphological Analysis ◽  
Pain Perception ◽  
Ex Vivo ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Neuroprotective Effects

The bioactive form of vitamin .D, 1,25-dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2-3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased β-galactosidase (B-gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator-activated-receptor-alpha (PPAR-α), reduced most of these effects. Morphological analysis of ex-vivo microglia obtained from vitamin-D-deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D.

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