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Benedikt L Nubaum, Josef Vogt, Ulrich Wachter, Oscar McCook, Martin Wepler, José Matallo, Enrico Calzia, Michael Gröger, Michael Georgieff, Mark E Wood, Matthew Whiteman, Peter Radermacher, Sebastian Hafner
Decreased levels of endogenous hydrogen sulfide (H2S) contribute to atherosclerosis, whereas equivocal data are available on H2S effects during sepsis. Moreover, H2S improved glucose utilization in anaesthetized, ventilated, hypothermic mice, but normothermia and/or sepsis blunted this effect. The metabolic effects of H2S in large animals are controversial. Therefore, we investigated the effects of the H2S donor GYY4137 during resuscitated, fecal peritonitis-induced septic shock in swine with genetically and diet-induced coronary artery disease (CAD)...
January 19, 2017: Shock
Nikolay Bazhanov, Olivier Escaffre, Alexander N Freiberg, Roberto P Garofalo, Antonella Casola
Hydrogen sulfide is an important endogenous mediator that has been the focus of intense investigation in the past few years, leading to the discovery of its role in vasoactive, cytoprotective and anti-inflammatory responses. Recently, we made a critical observation that H2S also has a protective role in paramyxovirus infection by modulating inflammatory responses and viral replication. In this study we tested the antiviral and anti-inflammatory activity of the H2S slow-releasing donor GYY4137 on enveloped RNA viruses from Ortho-, Filo-, Flavi- and Bunyavirus families, for which there is no FDA-approved vaccine or therapeutic available, with the exception of influenza...
January 20, 2017: Scientific Reports
Hong-Xia Zhang, Shu-Juan Liu, Xiao-Lu Tang, Guo-Li Duan, Xin Ni, Xiao-Yan Zhu, Yu-Jian Liu, Chang-Nan Wang
BACKGROUND: Hydrogen sulfide (H2S), known as the third endogenous gaseous transmitter, has received increasing attention because of its diverse effects, including angiogenesis, vascular relaxation and myocardial protection.We aimed to investigate the role of H2S in oxidative/nitrative stress and inflammation in acute lung injury (ALI) induced by endotoxemia. METHODS: Male ICR mice were divided in six groups: (1) Control group; (2) GYY4137treatment group; (3) L-NAME treatment group; (4) lipopolysaccharide (LPS) treatment group; (5) LPS with GYY4137 treatment group; and (6) LPS with L-NAME treatment group...
2016: Cellular Physiology and Biochemistry
Sachiko Juman, Yasuo Nara, Naomi Yasui, Hiroko Negishi, Hiroto Okuda, Nichika Takado, Tomohiro Miki
Stroke-prone spontaneously hypertensive rats (SHRSP/Izm; SHRSP) develop severe hypertension and die of cerebral stroke. However, the genetic mechanisms underlying their stroke susceptibility have not been clarified yet. In this study, we used astrocytes from the newborn brain cortex of spontaneously hypertensive rats (SHR/Izm; SHR) and SHRSP to find the difference of genetic characteristics. Astrocytes are known to have functions of vasodilation and nutrient uptake for neurons in the brain. The continuous generation of hydrogen peroxide (H2O2) dose-dependently causes cell death in astrocytes, and SHRSP was more vulnerable than SHR...
2016: Biological & Pharmaceutical Bulletin
Eberhard Grambow, Christian Leppin, Katja Leppin, Günther Kundt, Ernst Klar, Marcus Frank, Brigitte Vollmar
The volatile transmitter hydrogen sulfide (H2S) is known for its various functions in vascular biology. This study evaluates the effect of the H2S-donor GYY4137 (GYY) on thrombus stability and microvascular thrombolysis. Human whole blood served for all in vitro studies and was analyzed in a resting state, after stimulation with thrombin-receptor activating peptide (TRAP) and after incubation with 10 or 30 mM GYY or its vehicle DMSO following TRAP-activation, respectively. As a marker for thrombus stability, platelet-leukocyte aggregation was assessed using flow cytometry after staining of human whole blood against CD62P and CD45, respectively...
November 7, 2016: Platelets
I Lobb, J Jiang, D Lian, W Liu, A Haig, M N Saha, R Torregrossa, M E Wood, M Whiteman, A Sener
Ischemia-reperfusion injury (IRI) is unavoidably caused by loss and subsequent restoration of blood flow during organ procurement and prolonged IRI results in increased rates of delayed graft function and early graft loss. The endogenously produced gasotransmitter, hydrogen sulfide (H2 S), is a novel molecule that mitigates hypoxic tissue injury. The current study investigates the protective mitochondrial effects of H2 S during in vivo cold storage and subsequent renal transplantation (RTx) and in vitro cold hypoxic renal injury...
October 15, 2016: American Journal of Transplantation
S A Coavoy-Sánchez, L Rodrigues, S A Teixeira, A G Soares, R Torregrossa, M E Wood, M Whiteman, S K P Costa, M N Muscará
Hydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H2S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved...
October 6, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
J C van den Born, R Mencke, S Conroy, C J Zeebregts, H van Goor, J L Hillebrands
Atherosclerotic plaques are classically divided into stable and vulnerable plaques. Vulnerable plaques are prone to rupture with a risk for infarction. High intraplaque microvessel density predisposes to plaque vulnerability. Hydrogen sulfide (H2S) is a proangiogenic gasotransmitter which is endogenously produced by cystathionine γ-lyase (CSE), and is believed to have vasculoprotective effects. However, due to its proangiogenic effects, H2S may result in pathological angiogenesis in atherosclerotic plaques, thereby increasing plaque vulnerability...
October 6, 2016: Scientific Reports
Guoliang Meng, Yujiao Xiao, Yan Ma, Xin Tang, Liping Xie, Jieqiong Liu, Yue Gu, Ying Yu, Chung-Min Park, Ming Xian, Xin Wang, Albert Ferro, Rui Wang, Philip K Moore, Zhiren Zhang, Hong Wang, Yi Han, Yong Ji
BACKGROUND: Hydrogen sulfide (H2S) is a gasotransmitter that regulates multiple cardiovascular functions. Krüppel-like factor 5 (KLF5) exerts diverse functions in the cardiovascular system. Whether and how H2S regulates KLF5 in myocardial hypertrophy is unknown. METHODS AND RESULTS: In our study, hypertrophic myocardial samples in the clinic were collected and underwent histological and molecular biological analysis. Spontaneously hypertensive rats and neonatal rat cardiomyocytes were studied for functional and signaling responses to GYY4137, an H2S-releasing compound...
September 2016: Journal of the American Heart Association
Vítor S Fernandes, Paz Recio, Elvira López-Oliva, María Pilar Martínez, Ana Sofía Ribeiro, María Victoria Barahona, Ana Cristina Martínez, Sara Benedito, Ángel Agis-Torres, Alberto Cabañero, Gemma M Muñoz, Albino García-Sacristán, Luis M Orensanz, Medardo Hernández
Hydrogen sulfide (H2S) is a gasotransmitter employed for intra- and inter-cellular communication in almost all organ systems. This study investigates the role of endogenous H2S in nerve-evoked relaxation of pig terminal bronchioles with 260 μm medium internal lumen diameter. High expression of the H2S synthesis enzyme cystathionine γ-lyase (CSE) in the bronchiolar muscle layer and strong CSE-immunoreactivity within nerve fibers distributed along smooth muscle bundles were observed. Further, endogenous H2S generated in bronchiolar membranes was reduced by CSE inhibition...
September 4, 2016: Pulmonary Pharmacology & Therapeutics
Elena Fernandez Burguera, Rosa Meijide-Failde, Francisco J Blanco
Rheumatoid arthritis (RA) and osteoarthritis (OA) are widespread rheumatic diseases characterized by persistent inflammation and joint destruction. Hydrogen sulfide (H2S) is an endogenous gas with important physiologic functions in the brain, vasculature and other organs. Recent studies have found H2S to be a mediator in inflammatory joint diseases. H2S exhibited anti-inflammatory, anti-catabolic and/or anti-oxidant effects in rodent models of acute arthritis and in in vitro models using human synoviocytes and articular chondrocytes from RA and OA tissues...
August 29, 2016: Current Drug Targets
Zhiqiang Chen, Zhonghe Zhang, Dongdong Zhang, Hao Li, Zhongye Sun
BACKGROUND AND OBJECTIVE: Increasing studies suggest that miRNAs are served as responders and regulators for pathological change in human. miR-485-5p is such a miRNA that has been proved to be affected by spinal cord I/R injury. This study was to investigate the functional involvement and mechanism of miR-485-5p in sulfuretted hydrogen (H2S) protecting neural cell from injury. METHODS: In this study, serum tumor necrosis factor (TNF-α) and miR-485-5p were detected in 20 patients with spinal cord ischemia/reperfusion (I/R) injury and in 20 healthy control...
September 23, 2016: Biochemical and Biophysical Research Communications
Shanwen Chen, Dingfang Bu, Yuanyuan Ma, Jing Zhu, Lie Sun, Shuai Zuo, Ju Ma, Tengyu Li, Zeyang Chen, Youwen Zheng, Xin Wang, Yisheng Pan, Pengyuan Wang, Yucun Liu
Intestinal barrier injury has been reported to play a vital role in the pathogenesis of endotoxemia. This study aimed to investigate the protective effect of GYY4137, a newly synthesized H2S donor, on the intestinal barrier function in the context of endotoxemia both in vitro and in vivo. Caco-2 (a widely used human colon cancer cell line in the study of intestinal epithelial barrier function) monolayers incubated with lipopolysaccharide (LPS) or TNF-α/IFN-γ and a mouse model of endotoxemia were used in this study...
October 15, 2016: Biochemical Pharmacology
Nadiya Druzhyna, Bartosz Szczesny, Gabor Olah, Katalin Módis, Antonia Asimakopoulou, Athanasia Pavlidou, Petra Szoleczky, Domokos Gerö, Kazunori Yanagi, Gabor Törö, Isabel López-García, Vassilios Myrianthopoulos, Emmanuel Mikros, John R Zatarain, Celia Chao, Andreas Papapetropoulos, Mark R Hellmich, Csaba Szabo
Cystathionine-β-synthase (CBS) has been recently identified as a drug target for several forms of cancer. Currently no potent and selective CBS inhibitors are available. Using a composite collection of 8871 clinically used drugs and well-annotated pharmacological compounds (including the LOPAC library, the FDA Approved Drug Library, the NIH Clinical Collection, the New Prestwick Chemical Library, the US Drug Collection, the International Drug Collection, the 'Killer Plates' collection and a small custom collection of PLP-dependent enzyme inhibitors), we conducted an in vitro screen in order to identify inhibitors for CBS using a primary 7-azido-4-methylcoumarin (AzMc) screen to detect CBS-derived hydrogen sulfide (H2S) production...
November 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Hongyu Zhao, Rui Yan, Xiaogang Zhou, Fang Ji, Bing Zhang
Intestinal barrier involves in the pathogeny of inflammatory bowel disease (IBD) and hydrogen sulfide (H2S) has been reported to improve intestinal barrier integrity. Thus, this study investigated the effects of GYY4137, a slow-release H2S donor, on DSS-induced inflammation and intestinal dysfunction. In vitro model, cellular permeability was significantly increased and expression of tight junctions (ZO-1, Cauldin4, and Occludin) was downregulated in Caco-2 cells. GYY4137 treatment markedly attenuated DSS-induced inflammation and barrier dysfunction...
October 2016: International Immunopharmacology
Qutuba G Karwi, Matthew Whiteman, Mark E Wood, Roberta Torregrossa, Gary F Baxter
Exogenous hydrogen sulfide (H2S) protects against myocardial ischemia/reperfusion injury but the mechanism of action is unclear. The present study investigated the effect of GYY4137, a slow-releasing H2S donor, on myocardial infarction given specifically at reperfusion and the signalling pathway involved. Thiobutabarbital-anesthetised rats were subjected to 30min of left coronary artery occlusion and 2h reperfusion. Infarct size was assessed by tetrazolium staining. In the first study, animals randomly received either no treatment or GYY4137 (26...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Athanasia Chatzianastasiou, Sofia-Iris Bibli, Ioanna Andreadou, Panagiotis Efentakis, Nina Kaludercic, Mark E Wood, Matthew Whiteman, Fabio Di Lisa, Andreas Daiber, Vangelis G Manolopoulos, Csaba Szabó, Andreas Papapetropoulos
Hydrogen sulfide (H2S) is a signaling molecule with protective effects in the cardiovascular system. To harness the therapeutic potential of H2S, a number of donors have been developed. The present study compares the cardioprotective actions of representative H2S donors from different classes and studies their mechanisms of action in myocardial injury in vitro and in vivo. Exposure of cardiomyocytes to H2O2 led to significant cytotoxicity, which was inhibited by sodium sulfide (Na2S), thiovaline (TV), GYY4137 [morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate], and AP39 [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol5yl)phenoxy)decyl) triphenylphospho-nium bromide]...
September 2016: Journal of Pharmacology and Experimental Therapeutics
Mi Liu, Zhanjun Jia, Ying Sun, Aihua Zhang, Tianxin Yang
Accumulating evidence demonstrated that hydrogen sulfide (H2S) is highly involved in inflammation, oxidative stress, and apoptosis and contributes to the pathogenesis of kidney diseases. However, the role of H2S in cisplatin nephrotoxicity is still debatable. Here we investigated the effect of GYY4137, a novel slow-releasing H2S donor, on cisplatin nephrotoxicity in mice. Male C57BL/6 mice were pretreated with GYY4137 for 72 h prior to cisplatin injection. After cisplatin treatment for 72 h, mice developed obvious renal dysfunction and kidney injury as evidenced by elevated blood urea nitrogen (BUN) and histological damage...
2016: Mediators of Inflammation
Teodora Ivanciuc, Elena Sbrana, Maria Ansar, Nikolay Bazhanov, Csaba Szabo, Antonella Casola, Roberto P Garofalo
Hydrogen sulfide (H2S) is an endogenous gaseous transmitter whose role in the pathophysiology of several lung diseases has been increasingly appreciated. Our recent studies in vitro have shown, we believe for the first time, that H2S has an important antiviral and antiinflammatory activity in respiratory syncytial virus (RSV) infection, the leading cause of bronchiolitis and viral pneumonia in children. Our objective was to evaluate the therapeutic potential of GYY4137, a novel slow-releasing H2S donor, for the prevention and treatment of RSV-induced lung disease, as well as to investigate the role of endogenous H2S in a mouse model of RSV infection...
November 2016: American Journal of Respiratory Cell and Molecular Biology
Shouzhe Lin, Fazil Visram, Weihua Liu, Aaron Haig, Jifu Jiang, Amy Mok, Dameng Lian, Mark E Wood, Robert Torregrossa, Matthew Whiteman, Ian Lobb, Alp Sener
PURPOSE: Chronic obstructive uropathy can cause irreversible kidney injury, atrophy and inflammation, which can ultimately lead to fibrosis. Epithelial-mesenchymal transition is a key trigger of fibrosis that is caused by up-regulation of TGF-β1 (transforming growth factor-β1) and ANGII (angiotensin II). H2S is an endogenously produced gasotransmitter with cytoprotective properties. We sought to elucidate the effects of the slow-releasing H2S donor GYY4137 on chronic ureteral obstruction and evaluate the potential mechanisms...
May 10, 2016: Journal of Urology
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