scholarly journals The Role of the Signaling Pathways Involved in the Protective Effect of Exogenous Hydrogen Sulfide on Myocardial Ischemia-Reperfusion Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuangyu Lv ◽  
Xiaotian Li ◽  
Shizhen Zhao ◽  
Huiyang Liu ◽  
Honggang Wang
Keyword(s):  
Blood Flow ◽  
Hydrogen Sulfide ◽  
Signaling Pathways ◽  
Structural Changes ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Cell Swelling ◽  
Signal Pathways

Ischemia/reperfusion (I/R) injury refers to the functional and structural changes in the process of blood flow recovery after ischemia. In addition to ischemia, the blood flow recovery can also lead to very harmful damage, such as the obvious cell swelling and the irreversible cell necrosis. I/R injury is related with many diseases, including myocardial I/R injury. Myocardial I/R injury refers to the aggravation of ischemic myocardial tissue injury due to sudden disorder of blood circulation. Although there are many studies on myocardial I/R injury, the exact mechanism is not fully understood. Hydrogen sulfide (H2S), like carbon monoxide and nitric oxide, is an important gas signal molecule. It plays an important role in many physiological and pathological processes. Recent studies indicate that H2S can improve myocardial I/R injury, however, its mechanism is not fully understood, especially the involved signal pathways. In this review, we summarize the related researches about the role of the signaling pathways involved in the protective effects of exogenous H2S on myocardial I/R injury, so as to provide theoretical reference for the future in-depth researches.

Abstract T P87: Hydrogen Sulfide Enhances Neurogenesis through the IRAK-1/GSK3β/AKT Signaling Pathways after Ischemic Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Pradip K Kamat ◽  
Anuradha Kalani ◽  
Neetu Tyagi
Keyword(s):  
Hydrogen Sulfide ◽  
Signaling Pathways ◽  
Ventricular Zone ◽  
Ischemia Reperfusion ◽  
Analysis Data ◽  
Akt Signaling ◽  
Artery Occlusion ◽  
Cortical Region ◽  
Neuronal Function

Background and purpose: Increasing evidence signifying that inflammation has an ample role in the ischemia and; neurogenesis is somehow affected by inflammation. Current approved therapy for stroke is limited and new strategies need to be investigated. Hydrogen sulfide (H2S) showed neuro-protective however, role of H2S in stroke-induced neurogenesis is not known. Therefore, the present study was to determine the role of H2S in ischemia induced neurogenesis. Methods: To perform this study; we employed 8-10 weak old C57BL/6 mice with following groups: WT-Sham; WT+ ischemia reperfusion (IR) for 7 days; IR+GYY4137 (H2S donor, 30μM for 7 days; Intra peritoneal injection); and Sham+ GYY4137 (30μM for 7 day). Ischemia was created by the middle cerebral artery occlusion, (MCAO) for 50 min followed by reperfusion for 7 days. The brain tissue from different groups was used for biochemical, infarct area molecular and immunohistochemistry analysis. Data were analyzed by one way ANOVA followed by Tukey test. Results: We found increased protein expression of IRAK-1 (F=3, 27.01; P<.005), GSK3β 9 (F=3, 89.47; P<.005), p-AKT (F=3, 89.47; P<.005) and reduced expression of AKT p-AKT(F=3, 112.2; P<.005) in I/R group as compared to sham that indicates alteration of inflammatory signaling pathways. Further, we also found decreased level of Nestin (F=3, 35.32; P<.005), GFAP (F=3, 95.14; P<.001), NeuN (F=3, 123.4; P<.001), TUJ-1 (F=3, 112; P<.005), MAP-2 (F=3, 31.54; P<.0001), IL-6 (F=3, 55.7; p<.05) and BDNF (F=3, 166.5; P<.005) in cortical region of I/R group which indicates loss of neuronal function. Additionally, immunohistochemistry assay also revealed the loss of Nestin (P<.05), BDNF (P<.05), MAP-2 (P<.05) along with increased GSK-3β (P<.005) expression in sub ventricular zone (SVZ) and hippocampal region. Further, GYY4137 treatment for 7 days in ischemic group significantly restored the Nestin, GFAP, IL-6, NeuN, TUJ-1, MAP-2 and BDNF levels via regulating IRAK-1/GSK3β/AKT signaling pathways. Conclusion: Present study clearly demonstrate that H2S plays an important role in ischemia induced neurogenesis as well as protecting neuronal function through inhibition of IRAK1/GSK3β/AKT signaling pathways. Acknowledgement: This work was supported by NTHL107640-NT.

scholarly journals Hydrogen sulfide-mediated cardioprotection against ischemia reperfusion is linked to KATP channel for mitochondrial preservation but not for its distinct preference on interfibrillar mitochondria

2019 ◽  
Vol 14 (2) ◽  
pp. 107-115 ◽  
Author(s):  
Priyadharshini Chandrasekaran ◽  
Sriram Ravindran ◽  
Sri Rahavi Boovarahan ◽  
Gino A. Kurian
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Katp Channel ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rat Hearts ◽  
Significant Difference ◽  
Interfibrillar Mitochondria ◽  
Subsarcolemmal Mitochondria

Hydrogen sulfide has been shown to protect  myocardium against ischemia-reperfusion injury by preserving interfibrillar mitochondria functional activi-ties than subsarcolemmal mitochondria. In this study, the role of the KATP channel in modulating the mitochondrial subpopulations during the cardioprotection mediated by NaSH (H2S donor) was investigated. Isolated rat hearts were treated with mitochondrial KATP channel closer glibenclamide (10 μM)/opener diazoxide (0.8 mM) via Langendorff perfusion apparatus before ischemia-reperfusion. The results showed that NaSH pre-conditioning in presence of glibenclamide significantly improved cardiac recovery without any significant difference between interfibrillar mitochondria and subsarcolemmal mitochondria.  In conclusion, targeting KATP channel may not be good option to target interfibrillar mitochondria/subsarcolemmal mitochondria against ischemia-reperfusion injury.

The Role of Hydrogen Sulfide and H2S-donors in Myocardial Protection Against Ischemia/Reperfusion Injury

2018 ◽  
Vol 25 (34) ◽  
pp. 4380-4401 ◽  
Author(s):  
Valentina Citi ◽  
Eugenia Piragine ◽  
Lara Testai ◽  
Maria Cristina Breschi ◽  
Vincenzo Calderone ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Myocardial Protection ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

scholarly journals Cinaciguat, a novel activator of soluble guanylate cyclase, protects against ischemia/reperfusion injury: role of hydrogen sulfide

2012 ◽  
Vol 302 (6) ◽  
pp. H1347-H1354 ◽  
Author(s):  
Fadi N. Salloum ◽  
Anindita Das ◽  
Arun Samidurai ◽  
Nicholas N. Hoke ◽  
Vinh Q. Chau ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Cardiac Function ◽  
Infarct Size ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
New Zealand White Rabbits ◽  
Tetrazolium Staining

Cinaciguat (BAY 58–2667) is a novel nitric oxide (NO)-independent activator of soluble guanylate cyclase (sGC), which induces cGMP-generation and vasodilation in diseased vessels. We tested the hypothesis that cinaciguat might trigger protection against ischemia/reperfusion (I/R) in the heart and adult cardiomyocytes through cGMP/protein kinase G (PKG)-dependent generation of hydrogen sulfide (H2S). Adult New Zealand White rabbits were pretreated with 1 or 10 μg/kg cinaciguat (iv) or 10% DMSO (vehicle) 15 min before I/R or with 10 μg/kg cinaciguat (iv) at reperfusion. Additionally, adult male ICR mice were treated with either cinaciguat (10 μg/kg ip) or vehicle 30 min before I/R or at the onset of reperfusion (10 μg/kg iv). The PKG inhibitor KT5283 (KT; 1 mg/kg ip) or dl-propargylglycine (PAG; 50 mg/kg ip) the inhibitor of the H2S-producing enzyme cystathionine-γ-lyase (CSE) were given 10 and 30 min before cinaciguat. Cardiac function and infarct size were assessed by echocardiography and tetrazolium staining, respectively. Primary adult mouse cardiomyocytes were isolated and treated with cinaciguat before simulated ischemia/reoxygenation. Cinaciguat caused 63 and 41% reduction of infarct size when given before I/R and at reperfusion in rabbits, respectively. In mice, cinaciguat pretreatment caused a more robust 80% reduction in infarct size vs. 63% reduction when given at reperfusion and preserved cardiac function following I/R, which were blocked by KT and PAG. Cinaciguat also caused an increase in myocardial PKG activity and CSE expression. In cardiomyocytes, cinaciguat (50 nM) reduced necrosis and apoptosis and increased H2S levels, which was abrogated by KT. Cinaciguat is a novel molecule to induce H2S generation and a powerful protection against I/R injury in heart.

scholarly journals Targeting Ferroptosis against Ischemia/Reperfusion Cardiac Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 667
Author(s):  
José Lillo-Moya ◽  
Catalina Rojas-Solé ◽  
Diego Muñoz-Salamanca ◽  
Emiliano Panieri ◽  
Luciano Saso ◽  
...  
Keyword(s):  
Blood Flow ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Ischemic Heart ◽  
Myocardial Infarct Size

Ischemic heart disease is a leading cause of death worldwide. Primarily, ischemia causes decreased oxygen supply, resulting in damage of the cardiac tissue. Naturally, reoxygenation has been recognized as the treatment of choice to recover blood flow through primary percutaneous coronary intervention. This treatment is the gold standard therapy to restore blood flow, but paradoxically it can also induce tissue injury. A number of different studies in animal models of acute myocardial infarction (AMI) suggest that ischemia-reperfusion injury (IRI) accounts for up to 50% of the final myocardial infarct size. Oxidative stress plays a critical role in the pathological process. Iron is an essential mineral required for a variety of vital biological functions but also has potentially toxic effects. A detrimental process induced by free iron is ferroptosis, a non-apoptotic type of programmed cell death. Accordingly, efforts to prevent ferroptosis in pathological settings have focused on the use of radical trapping antioxidants (RTAs), such as liproxstatin-1 (Lip-1). Hence, it is necessary to develop novel strategies to prevent cardiac IRI, thus improving the clinical outcome in patients with ischemic heart disease. The present review analyses the role of ferroptosis inhibition to prevent heart IRI, with special reference to Lip-1 as a promising drug in this clinicopathological context.

scholarly journals The Regulatory Effects and the Signaling Pathways of Natural Bioactive Compounds on Ferroptosis

Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2952
Author(s):  
Shenshen Zhang ◽  
Ruizhe Hu ◽  
Yaping Geng ◽  
Ke Chen ◽  
Ling Wang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Bioactive Compounds ◽  
Ischemia Reperfusion Injury ◽  
Biological Activities ◽  
Ischemia Reperfusion ◽  
Organ Damage ◽  
Regulated Cell Death ◽  
Phospholipid Peroxidation ◽  
Regulatory Effects

Natural bioactive compounds abundantly presented in foods and medicinal plants have recently received a remarkable attention because of their various biological activities and minimal toxicity. In recent years, many natural compounds appear to offer significant effects in the regulation of ferroptosis. Ferroptosis is the forefront of international scientific research which has been exponential growth since the term was coined. This type of regulated cell death is driven by iron-dependent phospholipid peroxidation. Recent studies have shown that numerous organ injuries and pathophysiological processes of many diseases are driven by ferroptosis, such as cancer, arteriosclerosis, neurodegenerative disease, diabetes, ischemia-reperfusion injury and acute renal failure. It is reported that the initiation and inhibition of ferroptosis plays a pivotal role in lipid peroxidation, organ damage, neurodegeneration and cancer growth and progression. Recently, many natural phytochemicals extracted from edible plants have been demonstrated to be novel ferroptosis regulators and have the potential to treat ferroptosis-related diseases. This review provides an updated overview on the role of natural bioactive compounds and the potential signaling pathways in the regulation of ferroptosis.

scholarly journals Beneficial Role of Hydrogen Sulfide in Renal Ischemia Reperfusion Injury in Rats

2018 ◽  
Vol 59 (8) ◽  
pp. 960 ◽  
Author(s):  
Eun Kyung Choi ◽  
Sol Hee Park ◽  
Jung A Lim ◽  
Seong Wook Hong ◽  
Kyung Hwa Kwak ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Beneficial Role ◽  
Renal Ischemia Reperfusion Injury
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