DOCSLIB.ORG

N-Acetylcysteine Prevents Reactive Oxygen Species–Mediated Myocardial Stress in Patients Undergoing Cardiac Surgery

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
N-Acetylcysteine Prevents Reactive Oxygen Species–Mediated Myocardial Stress in Patients Undergoing Cardiac Surgery View metadata, citation and similar papers at core.ac.uk brought to you by CORE Tossios et al Cardiopulmonary Support and Physiology provided by Elsevier - Publisher Connector N-acetylcysteine prevents reactive oxygen species–mediated myocardial stress in patients undergoing cardiac surgery: Results of a randomized, double-blind, placebo-controlled clinical trial Paschalis Tossios, MDa Wilhelm Bloch, MDb Astrid Huebnera M. Reza Raji, MDa Fotini Dodos, MDc Oliver Klass, MDa Michael Suedkamp, MDa Stefan-Mario Kasper, MDd Martin Hellmich, PhDe Uwe Mehlhorn, MDa Objective: Reactive oxygen species have been shown to contribute to myocardial stress in patients undergoing cardiac surgery, as demonstrated ␣ by myocardial 8-iso-prostaglandin-F2 and nitrotyrosine formation. We hypothesized that the reactive oxygen species scavenger N-acetylcysteine attenuates reactive oxygen species–mediated myocardial stress in patients undergoing cardiac surgery. CSP Methods: Forty patients undergoing coronary artery surgery (mean age Ϯ SD, 66 Ϯ 9 years; 9 women and 31 men) were randomized to receive either N-acetylcysteine (100 mg/kg into cardiopulmonary bypass prime followed by infusion at 20 mg ⅐ kgϪ1 ⅐ hϪ1,nϭ 20) or placebo (n ϭ 20). Drs Tossios, Bloch, Huebner, Klass, and Mehlhorn Patients and clinical staff were blinded to group assignment. Transmural left ventricular biopsy specimens collected before and at the end of cardiopulmonary bypass were subjected to immunocytochemical staining ␣ against 8-iso-prostaglandin-F2 (primary measure) as an indicator for reactive oxygen species–mediated lipid peroxidation and nitrotyrosine (coprimary measure) as a marker for peroxynitrite-mediated tissue injury. Cardiomyocyte staining was From the Departments of Cardiothoracic quantitatively determined by using densitometry (in gray units). Global left ven- a b c Surgery, Anatomy, Cardiology, Anesthe- tricular function was measured on the basis of fractional area of contraction by using siology,d and Medical Statistics, Informat- ics, and Epidemiology,e University of Co- transesophageal echocardiography. logne, Cologne, Germany. Received for publication Oct 31, 2002; re- visions requested Feb 10, 2003; revisions Results: Patient characteristics in both groups were comparable. The change in left received Feb 11, 2003; accepted for publi- ventricular cardiomyocyte staining (end of cardiopulmonary bypass Ϫ before car- cation April 11, 2003. diopulmonary bypass) differed significantly between groups for both primary mea- Address for reprints: Uwe Mehlhorn, MD, ␣ Ϫ Ϯ Ϯ Department of Cardiothoracic Surgery, sures: 8-iso-prostaglandin-F2 , 1.8 7.5 gray units (mean SD, N-acetylcys- University of Cologne, Joseph-Stelzmann- teine group) versus 5.0 Ϯ 4.1 gray units (placebo group; 95% confidence interval, Str. 9, 50924 Cologne, Germany (E-mail: ϭ Ϫ Ϯ [email protected]). 2.6-11.0, P .003); nitrotyrosine, 6.4 10.0 gray units (N-acetylcysteine group) Ϯ Ͻ J Thorac Cardiovasc Surg 2003;126: versus 9.2 8.4 gray units (placebo group; 95% confidence interval, 9.4-21.7, P 1513-20 .001). Hemodynamics and clinical outcomes were comparable in both groups. Copyright © 2003 by The American Asso- ciation for Thoracic Surgery 0022-5223/2003 $30.00 ϩ 0 Conclusions: Reactive oxygen species scavenging with N-acetylcysteine attenuates doi:10.1016/S0022-5223(03)00968-1 myocardial oxidative stress in the hearts of patients subjected to cardiopulmonary bypass and cardioplegic arrest. The Journal of Thoracic and Cardiovascular Surgery ● Volume 126, Number 5 1513 Cardiopulmonary Support and Physiology Tossios et al eactive oxygen species (ROS), such as hy- use NAC, a precursor of reduced glutathione, because of its Ϫ droxyl radical (OH ), superoxide radical properties to both enhance intracellular glutathione synthe- Ϫ 16 (O2 ), hydrogen peroxide (H2O2), and per- sis and directly scavenge ROS. NAC has been in clinical Ϫ oxynitrite (ONOO ), the product of nitric use for more than 30 years, primarily as a mucolytic, and is Ϫ oxide (NO) binding to O2 , are thought to the gold standard for treatment of acetaminophen poison- mediate the reperfusion injury that charac- ing.16 In addition, NAC has recently been shown to reduce Rterizes metabolic, structural, and functional (stunning) myo- ROS-induced renal dysfunction in patients subjected to cardial damage associated with experimental myocardial radiographic contrast agents.17 ischemia and reperfusion.1-3 Clinical studies have provided indirect evidence for ROS-mediated stress, such as malon- Materials and Methods dialdehyde and lipid hydroxylperoxidase determination in Patients the blood of patients with acute myocardial infarction4 or After approval by the University of Cologne Human Ethics Com- those subjected to percutaneous transluminal coronary an- mittee, written informed consent was obtained from each patient gioplasty5,6 or coronary artery bypass surgery.7 We have during the preoperative interview. Forty patients (9 women and 31 recently provided direct evidence for ROS-mediated myo- men) scheduled for elective or urgent coronary artery bypass cardial stress associated with ischemia and reperfusion be- surgery (Table 1) were randomized into either the NAC group (n ␣ ϭ 20) or the placebo group (n ϭ 20) according to a computer- cause we demonstrated both 8-iso-prostaglandin-F2 and nitrotyrosine formation in left ventricular (LV) biopsy spec- generated allocation list (randomly permuted blocks of random size) provided by the Department for Medical Statistics, Informat- imens of patients subjected to cardioplegic arrest.8 8-Iso- ics, and Epidemiology, University of Cologne. NAC (Fluimucil) prostaglandin-F ␣ is the stable end product of arachidonic 2 and placebo were supplied in identical-looking glass vials contain- acid oxidation generated by ROS attacks on membrane ing either5gofNACper50mLorisotonic sodium chloride phospholipids.6,9 Nitrotyrosine represents the stable end CSP solution. The vials were sequentially numbered according to the product of cell membrane protein–bound tyrosine nitration random list and were supplied by the Pharmacy of the University Ϫ 10,11 by ONOO . These data indicate the clinical relevance of Cologne. Patients in the NAC group received 100 mg of NAC of ROS-mediated oxidative stress associated with ischemia per kilogram of body weight into the CPB prime, followed by and reperfusion and imply a rational basis for ROS scaven- intravenous infusion at 20 mg of NAC per kilogram of body gers as adjuncts to reperfusion strategies. weight per hour until the end of CPB, a regimen similar to that Although numerous experimental investigations have clinically used by Andersen and associates.15 The rationale for demonstrated that ROS scavenging attenuates myocardial administering NAC into the CPB prime and throughout CPB as ischemia-reperfusion injury,1 only a few clinical studies opposed to adding it to cardioplegia alone was 2-fold: first, we have addressed their ability to ameliorate myocardial injury administered NAC before cardioplegia because of its property to enhance intracellular glutathione synthesis,16 and second, we in- associated with cardiopulmonary bypass (CPB) and car- tended to have systemic NAC concentrations at the time of mas- dioplegic arrest. For example, pretreatment with allopurinol sive ROS production (ie, myocardial reperfusion after aortic cross- either alone or in combination with vitamins E and C has clamp release) because of NAC’s property to directly scavenge been suggested to improve patient outcome after coronary ROS.16 Patients in the placebo group received equivalent amounts artery surgery by reducing the level of plasma ROS activ- of placebo. The flow chart depicting the trial phases according to 7,12 ity or to improve neurocardiac protection in high-risk the Consolidated Standards of Reporting Trials (CONSORT) state- pediatric cardiac surgery with deep hypothermic circulatory ment18 is shown in Figure 1. Patients were subjected to CPB at arrest.13 Menasche and colleagues14 showed that the ROS- 32°Cto34°C, the aorta was crossclamped, and myocardial revas- scavenging iron chelator deferoxamine reduced the poly- cularization was performed during cardioplegic arrest by using morphonuclear neutrophil oxidative responsivness, and single-shot, antegrade, cold (4°C) crystalloid Bretschneider car- Andersen and associates15 demonstrated that the antioxidant dioplegia (Custodiol, Dr Ko¨hler Chemie). and ROS scavenger N-acetylcysteine (NAC) reduced the neutrophil oxidative burst response in patients subjected to Clinical Protocol CPB and cardioplegic arrest. However, none of these stud- After anesthesia induction and standard hemodynamic monitoring, ies directly investigated the effect of ROS scavenging on including Swan-Ganz pulmonary artery catheterization, a 5-MHz transesophageal echocardiography (TEE) probe was placed to pro- myocardial tissue alterations. vide a LV short-axis image at the midpapillary level. From the Therefore the purpose of our randomized, double-blind, TEE recordings, we derived the fractional area of contraction controlled clinical trial was to compare the effects of NAC (FAC) as a measure of LV ejection fraction.8,19 Before cannulation ␣ versus placebo on myocardial 8-iso-prostaglandin-F2 and for CPB, we recorded baseline measurements of all hemodynamic nitrotyrosine formation as indicators for direct ROS-medi- parameters, including cardiac output and a 1-minute TEE reading. ated myocardial alterations in the hearts of patients sub- At 10 to 15 minutes after separation
Load more

Recommended publications
  • Long-Term N-Acetylcysteine and L-Arginine Administration Reduces Endothelial Activation and Systolic Blood Pressure in Hypertensive Patients with Type 2 Diabetes
    Emerging Treatments and Technologies ORIGINAL ARTICLE Long-Term N-Acetylcysteine and L-Arginine Administration Reduces Endothelial Activation and Systolic Blood Pressure in Hypertensive Patients With Type 2 Diabetes 1 1 VALENTINO MARTINA, MD PAOLA MASSARENTI, MD ardiovascular complications repre- 1 1 ANDI MASHA, MD FABIO SETTANNI, PHD sent 80% of the causes of death in 1 2 VALENTINA RAMELLA GIGLIARDI, MD LARA DELLA CASA, PHD 1 patients with type 2 diabetes. Several OREDANA ROCATO MD 2 C L B , STEFANIA BERGAMINI, PHD causes may explain this mortality excess. 3 2 ENZO MANZATO, MD, PHD NNA ANNONE MD, PHD 1 A I , Among these, the decreased availability of ARRIGO BERCHIO, MD nitric oxide (NO) has increasingly gained credit. In fact, reduced NO availability has been demonstrated not only in diabe- OBJECTIVE — Reactive oxygen and nitric oxide (NO) have recently been considered to be tes (1) but also in other diseases, such as involved in the cardiovascular complications of patients with type 2 diabetes, as NO is thought atherosclerosis and hypertension, known to lose its beneficial physiological effects in the presence of oxygen radicals. For this reason, we to be associated with increased mortality tested the effects of L-arginine (ARG) and N-acetylcysteine (NAC) administration in increasing due to cardiovascular causes (2,3). NO is NO bioavailability by reducing free radical formation. crucial for regulating the vascular tone RESEARCH DESIGN AND METHODS — A double-blind study was performed on 24 and maintaining the intrinsic thrombore- male patients with type 2 diabetes and hypertension divided into two groups of 12 patients that sistant and atheroprotective properties of randomly received either an oral supplementation of placebo or NAC ϩ ARG for 6 months.
    [Show full text]
  • The Effect of N-Acetylcysteine on Amylase, Electrolytes, Vitamins and Nitrosative Stress Levels in Rats Treated with Maras Powder
    ORIGINAL ARTICLE East J Med 25(3): 378-382, 2020 DOI: 10.5505/ejm.2020.26680 The Effect of N-acetylcysteine on Amylase, Electrolytes, Vitamins and Nitrosative Stress Levels in Rats Treated with Maras Powder Velid Unsal1*, Ergul Belge Kurutas2 1Department of Nutrition and Dietetics, Faculty of Health Sciences, Mardin Artuklu University, Mardin, Turkey 2Department of Medical Biochemistry, Faculty of Medicine, Sutcu Imam University, Kahramanmaras, Turkey ABSTRACT The aim of this study is to investigate the effects of N-acetylcysteine (NAC) on amylase, electrolytes, vitamins and nitrosative stress levels in the plasma of rats treated with smokeless tobacco "maras powder". Our study consisted of three groups. Control (n = 10), the group using maras powder (n = 10), maras powder+ NAC group. To the Maras powder group, 200 mg maras powder was placed in the sublingual area under general anesthesia. It was waited for 15 minutes for Maras powder to be absorbed through mucosa. This procedure was repeated once a day and for 7 days. To the NAC group, 200 mg of Maras powder was given as in the Maras powder group and NAC was injected intraperitoneally with a dose of 100 mg / kg / day. On the 8th day, the levels of amylase, vitamins (A, C and E), electrolytes (Na+, K+, Cl-) and, as the biomarkers of nitrosative stress, nitric oxide (NO) and nitrotyrosine (3-NTx) in the plasma of all three groups were measured by the methods of ELISA. It was determined that amylase, 3-NTx, NO, electrolyte levels increased in the group using Maras powder compared to the control and NAC groups, but vitamin levels decreased.
    [Show full text]
  • Inhaled NO and Markers of Oxidant Injury in Infants with Respiratory Failure
    Original Article Inhaled NO and Markers of Oxidant Injury in Infants with Respiratory Failure Krisa P. Van Meurs, MD INTRODUCTION Toby L. Cohen, MD Term infants experience substantial morbidity and mortality from Guang Yang, PhD respiratory failure.1,2 This condition can result from meconium Marco Somaschini, MD aspiration or infection complicated by persistent pulmonary 3 Pavani Kuruma, MD hypertension of the newborn among other causes. Recent clinical Phyllis A. Dennery, MD trials have demonstrated that the endogenous vasodilator nitric oxide (NO) may be a useful adjunct in the treatment of term infants with respiratory failure and decreases the need for extracorporeal membrane oxygenation.4–6 Despite the known BACKGROUND: benefits of iNO, there are also theoretical considerations as to the Inhaled nitric oxide (iNO) is an effective adjunct in the treatment of effects of NO on oxidative stress since NO can combine with infants with respiratory failure. Although there are clear benefits to this molecular oxygen to form nitrogen dioxide at a rate dependent on therapy, potential toxicity could result from reactive nitrosylated species. the concentration of oxygen and the square of the concentration of NO.7,8 Additionally, NO can react with superoxide radicals to form a OBJECTIVE: To evaluate whether iNO therapy is associated with increased serum secondary stable cytotoxic species, peroxynitrite, which eventually markers of oxidative stress. decomposes to NO and the hydroxyl radical, a highly toxic and reactive molecule.9 In animals, the combination of oxygen with DESIGN/METHOD: NO resulted in increased toxicity in a ventilated piglet model.9 In Multiple markers were prospectively evaluated in the serum of term contrast, NO significantly reduced oxygen toxicity at low doses (5 to infants with severe respiratory failure treated with iNO for 1 to 72 hours.
    [Show full text]
  • On the Liquid Chemistry of the Reactive Nitrogen Species Peroxynitrite and Nitrogen Dioxide Generated by Physical Plasmas
    biomolecules Article On the Liquid Chemistry of the Reactive Nitrogen Species Peroxynitrite and Nitrogen Dioxide Generated by Physical Plasmas Giuliana Bruno 1, Sebastian Wenske 1, Jan-Wilm Lackmann 2, Michael Lalk 3 , Thomas von Woedtke 4 and Kristian Wende 1,* 1 Centre for Innovation Competence (ZIK) Plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), 17489 Greifswald, Germany; [email protected] (G.B.); [email protected] (S.W.) 2 Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany; [email protected] 3 Institute of Biochemistry, University of Greifswald, 17487 Greifswald, Germany; [email protected] 4 Leibniz Institute for Plasma Science and Technology, 17489 Greifswald, Germany; [email protected] * Correspondence: [email protected] Received: 9 November 2020; Accepted: 9 December 2020; Published: 16 December 2020 Abstract: Cold physical plasmas modulate cellular redox signaling processes, leading to the evolution of a number of clinical applications in recent years. They are a source of small reactive species, including reactive nitrogen species (RNS). Wound healing is a major application and, as its physiology involves RNS signaling, a correlation between clinical effectiveness and the activity of plasma-derived RNS seems evident. To investigate the type and reactivity of plasma-derived RNS in aqueous systems, a model with tyrosine as a tracer was utilized. By high-resolution mass spectrometry, 26 different tyrosine derivatives including the physiologic nitrotyrosine were identified. The product pattern was distinctive in terms of plasma parameters, especially gas phase composition. By scavenger experiments and isotopic labelling, gaseous nitric dioxide radicals and liquid phase peroxynitrite ions were determined as dominant RNS.
    [Show full text]
  • Effects of Postresuscitation N-Acetylcysteine on Cerebral Free Radical Production and Perfusion During Reoxygenation of Hypoxic Newborn Piglets
    0031-3998/08/6403-0256 Vol. 64, No. 3, 2008 PEDIATRIC RESEARCH Printed in U.S.A. Copyright © 2008 International Pediatric Research Foundation, Inc. Effects of Postresuscitation N-Acetylcysteine on Cerebral Free Radical Production and Perfusion During Reoxygenation of Hypoxic Newborn Piglets TZE-FUN LEE, CORINNE N. TYMAFICHUK, DAVID L. BIGAM, AND PO-YIN CHEUNG Department of Pediatrics [T.-F.L., C.N.T., P.-Y.C.], Department of Surgery [D.L.B.], University of Alberta, Edmonton, Alberta, Canada T6G 2E1 ABSTRACT: Hydrogen peroxide (H2O2) and nitric oxide (NO) oxidant, has been shown to have certain beneficial effects on contribute to the pathogenesis of cerebral hypoxic-ischemic injury. neuronal protection after I-R or H-R (2,3). Administration of We evaluated the neuroprotective effect of N-acetyl-L-cysteine NAC has been shown to reduce cerebral injury in adult rats (NAC, a free radical scavenger) against oxidative stress and perfu- with I-R (2) and neonatal rats with lipopolysaccharide- sion in a model of neonatal hypoxia-reoxygenation (H-R). Piglets sensitized hypoxia-ischemia (3). We previously reported that (1–3 d, 1.6–2.3 kg) were randomized into a sham-operated group postresuscitation treatment with NAC reduced cerebral H O (without H-R) (n ϭ 5) and two H-R experimental groups (2 h 2 2 normocapnic alveolar hypoxia followed by 4 h reoxygenation) (n ϭ production as well as lipid peroxidation in moderately hypoxic 7/group). Five minutes after reoxygenation, piglets were given either newborn piglets after2hofreoxygenation (4). i.v. saline (H-R controls) or NAC (30 mg/kg bolus then 20 mg/kg/h Other than H2O2, there is substantial evidence supporting the infusion) in a blinded-randomized fashion.
    [Show full text]
  • (NT), a Nitrosative Stress Biomarker, Plasma Concentrations in Gallstone
    ANTICANCER RESEARCH 39 : 809-814 (2019) doi:10.21873/anticanres.13179 Nitrotyrosine (NT), a Nitrosative Stress Biomarker, Plasma Concentrations in Gallstone Disease and Cancer Patients IINA SAIMANEN 1, DINA RAHKOLA 1, VIIVI KUOSMANEN 1, JARI KÄRKKÄINEN 1, TUOMAS SELANDER 2, ANU HOLOPAINEN 3, SAMULI ASPINEN 1 and MATTI ESKELINEN 1 1Department of Surgery, Kuopio University Hospital and School of Medicine, University of Eastern Finland, Kuopio, Finland; 2Department of Science Service Center, Kuopio University Hospital, Kuopio, Finland; 3Department of Clinical Chemistry, Eastern Finland Laboratory Center, Kuopio, Finland Abstract. Background/Aim: The aim of this study was to assess Since NT is the end product of ONOO – oxidation, assessment the plasma concentration of the nitrosative stress biomarker of plasma NT concentration could be a useful biomarker of nitrotyrosine (NT) in gallstone disease and cancer patients. nitrosative stress status in patients who underwent surgery for Materials and Methods: Initially, 114 patients with symptomatic cholelithiasis. Our original hypothesis was that no difference gallstone disease were randomized into the laparoscopic in oxidative stress (OS) between the laparoscopic cholecystectomy (LC) (n=54) and the minicholecystectomy (MC) cholecystectomy (LC) and minicholecystectomy (MC) (n=60) groups. The plasma concentrations of NT were measured procedures would be detected (4). Our results suggest that both just before, immediately after (POP1) and 6 h after operation LC and MC are safe and feasible operations and have a quite (POP2). The cancer patients of this study included ten patients similar short- and long-term outcome (4, 5). Interestingly, the with gastrointestinal cancer and 19 patients with gynecological LC patients had significantly shorter convalescence and lower cancer.
    [Show full text]
  • Red Cabbage Anthocyanins As Inhibitors of Lipopolysaccharide
    International Journal of Biological Macromolecules 80 (2015) 702–709 Contents lists available at ScienceDirect International Journal of Biological Macromolecules j ournal homepage: www.elsevier.com/locate/ijbiomac Red cabbage anthocyanins as inhibitors of lipopolysaccharide-induced oxidative stress in blood platelets a,b a,∗ c a Joanna Saluk , Michal Bijak , Malgorzata M. Posmyk , Halina M. Zbikowska a Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland b Department of Toxicology, Faculty of Pharmacy with Division of Medical Analytics, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland c Department of Ecophysiology and Plant Development, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland a r a t i c l e i n f o b s t r a c t Article history: LPS is a Gram-negative bacteria endotoxin, which is an important pro-inflammatory agent. Blood platelets Received 12 May 2015 take part both in inflammatory processes and in pathogenesis of septic shock following accumulation Received in revised form 6 July 2015 of LPS. As a platelet agonist LPS causes the intraplatelet overproduction of ROS/RNS that are responsible Accepted 18 July 2015 for adverse modifications in the structure of platelet compounds being associated with a development Available online 21 July 2015 of platelet-dependent diseases. Existing evidence suggests that anthocyanins (ATH) are able to protect the circulatory system. The Keywords: antioxidative properties of ATH are believed to be mainly responsible for their positive health effects. Lipopolysaccharide The main goal of the present in vitro study was to investigate the potential protective properties of red Red cabbage Platelets cabbage ATH against oxidative damage induced by LPS in blood platelets.
    [Show full text]
  • Protective Role of Glutathione and Role of Nitric Oxide Production in the Pathogenesis of Pterygium
    Protective Role Of Glutathione And Role Of Nitric Oxide Production In The Pathogenesis Of Pterygium Fidelina Parra Instituto Politecnico Nacional Escuela Superior de Medicina Alexandre Kormanovski ( [email protected] ) Instituto Politecnico Nacional Escuela Superior de Medicina https://orcid.org/0000-0001-8731-0527 Gustavo Guevara-Balcazar Instituto Politecnico Nacional Escuela Superior de Medicina Maria del Carmen Castillo-Hernández Instituto Politecnico Nacional Escuela Superior de Medicina Antonio Franco-Vadillo Instituto Politecnico Nacional Escuela Superior de Medicina Mireille Toledo-Blas Instituto Politecnico Nacional Escuela Superior de Medicina Rosa Adriana Jarillo-Luna Instituto Politecnico Nacional Escuela Superior de Medicina Eleazar Lara-Padilla Instituto Politecnico Nacional Escuela Superior de Medicina Research article Keywords: pterygium, glutathione, nitric oxide, endothelial nitric oxide synthase, gender differences Posted Date: May 13th, 2020 DOI: https://doi.org/10.21203/rs.2.17704/v2 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/15 Abstract Background: In the pathogenesis of pterygium, the protective role of glutathione and nitric oxide production is unclear. These are important factors for homeostasis in the redox state of cells. The aim of this study was to determine the levels of these and related parameters in pterygium tissue. Methods: Five groups of tissue samples were examined: control, primary pterygium, recurrent pterygium and two groups of primary pterygium given a one-month NAC pre-surgery treatment (topical or systemic). The levels of endothelial nitric oxide synthase (e-NOS), nitric oxide (NO), 3-nitrotyrosine (3NT), reduced and oxidized glutathione (GSH and GSSG), and catalase (CAT) were evaluated in tissue homogenates.
    [Show full text]
  • Glutathione and Nitric Oxide: Key Team Players in Use and Disuse of Skeletal Muscle
    nutrients Review Glutathione and Nitric Oxide: Key Team Players in Use and Disuse of Skeletal Muscle Sara Baldelli 1 , Fabio Ciccarone 1, Dolores Limongi 1 , Paola Checconi 1 , Anna Teresa Palamara 2,3 and Maria Rosa Ciriolo 2,4,* 1 IRCCS San Raffaele Pisana, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy; [email protected] (S.B.); [email protected] (F.C.); [email protected] (D.L.); [email protected] (P.C.) 2 IRCCS San Raffaele ‘La Pisana’, 00166 Rome, Italy; [email protected] 3 Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy 4 Department of Biology, University of Rome “Tor Vergata”, 00133 Rome, Italy * Correspondence: [email protected]; Tel.: +39-06-7259-4369 Received: 31 July 2019; Accepted: 16 September 2019; Published: 30 September 2019 Abstract: Glutathione (GSH) is the main non-enzymatic antioxidant playing an important role in detoxification, signal transduction by modulation of protein thiols redox status and direct scavenging of radicals. The latter function is not only performed against reactive oxygen species (ROS) but GSH also has a fundamental role in buffering nitric oxide (NO), a physiologically-produced molecule having-multifaceted functions. The efficient rate of GSH synthesis and high levels of GSH-dependent enzymes are characteristic features of healthy skeletal muscle where, besides the canonical functions, it is also involved in muscle contraction regulation. Moreover, NO production in skeletal muscle is a direct consequence of contractile activity and influences several metabolic myocyte pathways under both physiological and pathological conditions.
    [Show full text]
  • Reduced Levels of S-Nitrosothiols in Plasma of Patients with Systemic Sclerosis and Raynaud's Phenomenon
    Vascular Pharmacology 63 (2014) 178–181 Contents lists available at ScienceDirect Vascular Pharmacology journal homepage: www.elsevier.com/locate/vph Reduced levels of S-nitrosothiols in plasma of patients with systemic sclerosis and Raynaud's phenomenon Devi Kundu ⁎, David Abraham, Carol M. Black, Christopher P. Denton, K. Richard Bruckdorfer Centre for Rheumatology and Connective Tissue Diseases, UCL Medical School, London NW3 2PF, UK article info abstract Article history: Objective: S-Nitrosothiols (RSNOs) are bioactive forms of nitric oxide which are involved in cell signalling and redox Received 14 January 2014 regulation of vascular function. Circulating S-nitrosothiols are predominantly in the form of S-nitrosoalbumin. In Received in revised form 3 September 2014 this study plasma concentrations of S-nitrosothiols were measured in patients with systemic sclerosis (SSc) Accepted 7 September 2014 where NO metabolism is known to be abnormal. Available online 15 October 2014 Patients and methods: Venous blood was collected from 16 patients with Raynaud's phenomenon (RP), 45 with systemic sclerosis (SSc) (34 patients had limited SSc (IcSSc) and 11 diffuse cutaneous disease (dcSSc)). Twenty Chemical compounds studied in this article: N-ethylmaleimide (PubChem ClD:4362) six healthy subjects were used as controls. Plasma S-nitrosothiol concentrations were measured by chemilumines- Acetic acid (PubChem: ClD:176) cence. The measurements were related to the extent of biological age, capillary/skin scores and disease duration. Potassium iodide (PubChem ClD: 4875) Results: Plasma RSNO levels in patients with Raynaud's phenomenon (RP) and in those with SSc was significantly Nitric oxide (PubChem: ClD: 145068) lower compared to the concentrations in control subjects.
    [Show full text]
  • 3-Nitrotyrosine Quantification Methods: Current Concepts and Future Challenges
    3-Nitrotyrosine quantification methods: Current concepts and future challenges * Dulce Teixeira a, Rúben Fernandes a, b, Cristina Prudencio^ a, b,Monica Vieira a, b, a Ci^encias Químicas e das Biomoleculas, Centro de Investigaçao~ em Saúde e Ambiente, Escola Superior de Tecnologia da Saúde do Porto, Instituto Politecnico do Porto, Portugal b I3S e Instituto de Investigaçao~ e Inovaçao~ em Saúde, Universidade do Porto, Portugal abstract Background: Measurement of 3-nitrotyrosine (3-NT) in biological samples can be used as a biomarker of nitrosative stress, since it is very stable and suitable for analysis. Increased 3-NT levels in biological samples have been associated with several physiological and pathological conditions. Different methods have been described for the detection and quantification of this molecule, such as (i) immunological methods; (ii) liquid chromatography, namely high-pressure liquid chromatography (HPLC)-based methods that use ultraviolet-visible (UV/VIS) absorption, electrochemical (ECD) and diode array (DAD) detection, liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS); (iii) gas chromatography, such as gas chromatography-mass spectrometry (GC-MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS). Methods: A literature review on nitrosative stress, protein nitration, as well as 3-NT quantification methods was carried out. Results: This review covers the different methods for analysis of 3-NT that have been developed during the last years as well as the latest advances in this field. Overall, all methods present positive and negative aspects, although it is clear that chromatography-based methods present good sensitivity and specificity. Regarding this, GC-based methods exhibit the highest sensibility in the quantification of 3-NT, although it requires a prior time consuming derivatization step.
    [Show full text]
  • Isobutyl Nitrite, Β-Picoline, and Some Acrylates Volume 122
    ISOBUTYL NITRITE, β-PICOLINE, AND SOME ACRYLATES VOLUME 122 This publication represents the views and expert opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, which met in Lyon, 5–12 June 2018 LYON, FRANCE - 2019 IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS ISOBUTYL NITRITE 1. Exposure Data Boiling point: 66–67 °C (experimental) Flash point: –21 °C (experimental) 1.1 Identification of the agent Density: 0.87 g/mL (experimental) Refractive index: 1.373 1.1.1 Nomenclature Relative density (water = 1): 0.87 g/cm3 Chem. Abstr. Serv. Reg. No.: 542-56-3 Vapour pressure: 10 mm Hg [1.3 kPa] at 20 °C IUPAC systematic name: 2-methylpropyl Water solubility: slightly soluble and gradu- nitrite ally decomposed by water: 935.9 mg/L, that Other names and abbreviations: IBN; is, < 1 mg/mL (estimated) iso-butyl nitrite; nitrous acid; isobutyl ester; Conversion factor: 1 ppm = 4.22 mg/m3 (at nitrous acid; 2-methylpropyl ester 1 atm and 25 °C). From Royal Society of Chemistry (2018). 1.1.4 Technical products and impurities 1.1.2 Structural and molecular formulae, and Analysis of commercially available isobutyl relative molecular mass nitrite revealed a purity of only 63%. The major impurity was isobutyl alcohol, formed as a result CH3 of degradation of the parent isobutyl nitrite O O (Maickel, 1988). H3C N 1.2 Production and use Molecular formula: C4H9NO2 Relative molecular mass: 103.12 1.2.1 Production process Isobutyl nitrite is synthesized by reacting 1.1.3 Chemical and physical properties isobutyl alcohol with sodium nitrite in dilute sulfuric acid (NTP, 1996).
    [Show full text]