DOCSLIB.ORG

AFRICA CARDIOVASCULAR JOURNAL of AFRICA • Volume 28, No 6, November/December 2017 389

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
AFRICA CARDIOVASCULAR JOURNAL of AFRICA • Volume 28, No 6, November/December 2017 389 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 6, November/December 2017 389 The effect of iloprost and sildenafil, alone and in combination, on myocardial ischaemia and nitric oxide and irisin levels Suna Aydin, Tuncay Kuloglu, Suleyman Aydin, Meltem Yardim, Davut Azboy, Zeki Temizturk, Ali Kemal Kalkan, Mehmet Nesimi Eren Abstract sacrificed after 24 hours, and their heart, liver and kidney tissues and blood samples were collected for analyses. An Aim: Insufficient oxygen supply to organs and tissues due to immunohistochemical method was used to measure the change reduced arterial or venous blood flow results in ischaemia, in irisin levels, the ELISA method to quantify blood irisin during which, although ATP production stops, AMP and levels, and Griess’ assay to determine nitric oxide (NO) levels adenosine continue to be produced from ATP. The fate of in the serum and tissue. Myocardial ischaemia was confirmed irisin, which causes the production of heat instead of ATP based on the results of Masson’s trichrome staining, as well as during ischaemia, is unknown. Iloprost and sildenafil are levels of troponin and creatine kinase MB. two pharmaceutical agents that mediate the resumption of Results: Irisin levels in biological tissue and serum dropped reperfusion (blood supply) via vasodilatation during ischae- statistically significantly in the ischaemic group (MI), but mic conditions. Our study aimed to explore the effects of were restored with ILO and SIL administration. Individual iloprost and sildenafil on irisin levels in the heart, liver and SIL administration was more potently restorative than indi- kidney tissues and whether these pharmaceutical agents had vidual ILO administration or the combined administration any impact on serum irisin and nitric oxide levels in rats with of the two agents. NO level, on the other hand, showed the induced experimental myocardial ischaemia. opposite tendency, reaching the highest level in the MI group, Methods: The study included adult male Sprague-Dawley rats and falling with the use of pharmaceutical agents. aged 10 months and weighing between 250 and 280 g. The Conclusions: Individual or combined administration of ILO animals were randomly allocated to eight groups, with five rats and SIL reduced myocardial ischaemia and NO levels, and in each group. The groups were: sham (control), iloprost (ILO), increased irisin levels. Elevated levels of irisin obtained by sildenafil (SIL), ILO + SIL, myocardial ischaemia (MI), MI + drug administration could possibly contribute to accelerated ILO, MI + SIL and MI + ILO + SIL. The treatment protocols wound recovery by local heat production. Sildenafil was more were implemented before inducing ischaemia, which was done effective than iloprost in eliminating ischaemia and may be the by occluding the left coronary artery with a plastic ligature for first choice in offsetting the effects of ischaemia in the future. 30 minutes. Following the reperfusion procedure, all rats were Keywords: iloprost, sildenafil, nitric oxide, irisin, myocardial Department of Cardiovascular Surgery, Elazig Education ischaemia–reperfusion and Research Hospital, Health Science University, Elazig, Turkey Submitted 2/11/16, accepted 25/4/17 Suna Aydin, MD, [email protected] Published online 31/8/17 Davut Azboy, MD Cardiovasc J Afr 2017; 28: 389–396 www.cvja.co.za Zeki Temizturk, MD Department of Anatomy, School of Medicine, Firat DOI: 10.5830/CVJA-2017-025 University, Elazig, Turkey Suna Aydin, MD Myocardial ischaemia impairs the function and survival of Department of Histology and Embryology, School of cardiac myocytes. Current treatment for this condition is Medicine, Firat University, Elazig, Turkey elimination of ischaemia.1 Although the use of coronary dilator Tuncay Kuloglu, MD anti-aggregatory medications to various degrees is the treatment 2,3 Department of Medical Biochemistry (Firat Hormones of choice in the elimination of ischaemia, surgical coronary Research Group), School of Medicine, Firat University, bypass methods are also used, as laid down in treatment Elazig, Turkey guidelines.4-6 Additionally, iloprost is the first line of treatment in Suleyman Aydin, PhD occlusions seen in peripheral artery disease.7 Meltem Yardim, MD Iloprost (ILO) is an eicosanoid pharmaceutical agent from Department of Cardiology, Education and Research the prostacyclin group.8 Currently, it is clinically used to unblock Hospital, Istanbul, Turkey occluded vessels.9,10 ILO exercises its vasodilatory effect by Ali Kemal Kalkan, MD preventing platelet aggregation.8,11 Another vasodilatory agent 12 Department of Cardiovascular Surgery, School of that acts via nitric oxide (NO) is sildenafil (SIL). NO levels 13 Medicine, Dicle University, Diyarbakir, Turkey increase during ischaemia. During reperfusion, NO levels Mehmet Nesimi Eren, MD are elevated,13 caused by the vasodilator effect of SIL.14 The - increased NO levels combine with a superoxide radical (O2 ) to 390 CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 6, November/December 2017 AFRICA form a toxic oxygen metabolite, peroxynitrite (ONOO-), which ILO in the 0.2–2-μg/kg range.26,27 In this study, 2 mg/kg sildenafil causes damage in the tissues.15,16 Therefore, elucidation of the citrate was administered to the SIL group and 1 μg/kg to the changes in NO levels caused by the administration of ILO and ILO group via the intraperitoneal route before the induction of SIL, which were used for the reperfusion of tissues, could help ischaemia–reperfusion, as described previously by Harada et al.28 explain the mechanisms underlying this process. A 30-minute occlusion was then induced using a plastic ligature, At present, sildenafil is employed to correct erectile dysfunction.12 as described previously.29 After the ligature was released, blood Since it acts as a vasodilator, it can serve as a therapeutic agent flow was visually confirmed. All rats were sacrificed at 24 hours during ischaemia.14 Vasodilatation enhances oxygenation and following the reperfusion procedure. therefore mediates in the elimination of ischaemia and increases Blood samples were collected as described for previous adenosine triphosphate (ATP) formation. It is established that experiments,30 centrifuged at 4 000 rpm and stored at –80°C until the aerobic ATP formation is blocked in hypoxic states. Therefore, irisin analysis. Glucose, creatine kinase (CK), creatine kinase MB ischaemia leads to a decrease in ATP production.17 Another (CKMB) and troponin I on the other hand, were analysed without molecule that causes a reduction in ATP levels is irisin.18,19 By delay on an auto-analyser. Heart, liver and kidney tissue was fixed increasing the amount of uncoupling proteins, this molecule leads in 10% formaldehyde solution and stored for immunohistochemical to the release of heat rather than ATP from molecules.18 analysis. The remaining heart, liver and kidney tissue, after the wet Since ILO,7 used in ischaemic peripheral artery disease, and weight was determined, were homogenised and the supernatants SIL,12 used in erectile dysfunction, increase oxygenation through were stored at –80°C for NO analysis. vasodilatation, the tissues recovered from ischaemia would As its half life is short, it is difficult to directly analyse NO. For theoretically be expected to have elevated ATP levels. On the NO measurements, its stable end-products, nitrite and nitrate, other hand, in the presence of irisin, heat production would are quantified in tissues with a spectrophotometric method. This increase through uncoupling of proteins and cause a decrease method is based on the principle of measuring the absorbance at in ATP production.18,19 Therefore there seems to be an obvious 545 nm of the complex formed when nitrate is reduced to nitrite correlation between the treatment of ischaemic tissue with ILO in the presence of nitrate reductase enzyme, and the resulting and SIL, and irisin levels. nitrite reacts with sulfanylamide and N-ethylendiamin.31 Furthermore, myocardial ischaemia does not only affect Serum irisin levels were determined using the ELISA method, heart tissue. It was reported in previous studies that myocardial following the catalogue guidelines provided by the manufacturing ischaemia could directly impact on kidney tissue,20 which is an firm.32 The kit was reported to have a minimum irisin detection excretory organ, and the liver,21 where glycogenesis takes place. limit of 1.29 ng/ml and minimal cross-reactivity (~9%) with In addition, there is an increased need for energy (glucose) fibronectin type III domain-containing protein 5 (FNDC5). In during ischaemic conditions. It was reported that irisin inhibited our laboratory results, we found an intra-assay value of 8% and glycogenesis, or impeded the production of glucose.22 inter-assay value of 10%. Therefore the aim of this study was to determine the change in Histopathological examinations were carried out using the irisin level in tissues with increased energy needs under ischaemic triphenyl tetrazolium chloride method to identify the damage conditions. Our principal objectives were to explore (1) whether to the myocardium and other tissues, as described previously.23 ILO and SIL played a part in recovery after myocardial injury Myocardial injury was assessed according to the semi-quantitative and how they changed irisin expression in experimentally induced method of Miller et al.33 The Abc immunohistochemical method myocardial ischaemia–reperfusion; (2) whether ILO, SIL, or of Hsu et al.34 was used to determine the distribution of irisin a combination of both were more efficient in the treatment of expression in the myocardium and other tissues.34 ischaemic injury; (3) how NO levels were altered in response to these therapeutic agents; (4) whether irisin, which causes metabolisation of ATP, was down- or upregulated in tissues with Statistical analysis an increased need for ATP, as in the case of ischaemia; and (5) The extent of the damage in the myocardium and other tissues how ILO and SIL treatment affected irisin expression in heart, was determined using the Student’s t-test. SPSS 22 software liver and kidney tissues under ischaemic conditions. was employed in all statistical analyses.
Load more

Recommended publications
  • Nitrate Reductase-Dependent Nitric Oxide Synthesis in the Defense Response of Arabidopsis Thaliana Against Pseudomonas Syringae
    Tropical Plant Pathology, vol. 35, 2, 104-107 (2010) Copyright by the Brazilian Phytopathological Society. Printed in Brazil www.sbfito.com.br SHORT COMMUNICATION / COMUNICAÇÃO Nitrate reductase-dependent nitric oxide synthesis in the defense response of Arabidopsis thaliana against Pseudomonas syringae Halley C. Oliveira, Elzira E. Saviani, Jusceley F. P. Oliveira & Ione Salgado Departamento de Biologia Vegetal, Instituto de Biologia, Universidade Estadual de Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil Author for correspondence: Ione Salgado, e-mail: [email protected] ABSTRACT Nitrate reductase (NR) was recently shown to play an important role during phytopathogenic interactions by providing substrates for the synthesis of nitric oxide (NO), a key signal for plant defense responses. In order to give additional support to this hypothesis, we compared NO-mediated defense responses of wild-type and NR double-deficient (nia1 nia2) Arabidopsis thaliana plants inoculated with the IBSBF-1115 (ibs) strain of Pseudomonas syringae pv. maculicola (Psm) and with genetically characterized avirulent (avr) or virulent (vir) strains of Psm. Inoculation of wild-type leaves with avr or ibs, but not vir, stimulated NO emission, as measured by the indicator 4,5-diaminofluorescein. NO emission induced by avr was higher than that induced by ibs. Wild-type plants displayed the hypersensitive response (HR) when infiltrated with the strains avr or ibs, although a stronger HR was induced by avr. The vir strain did not induce HR in wild-type plants, and leaves developed severe infection symptoms. nia1 nia2 plants did not show significantly increased NO emission nor did they develop HR to any of the analyzed strains of Psm, but displayed clorotic lesions and higher bacterial growth in their leaves.
    [Show full text]
  • The Availability of Organic Nitrates from Intravenous Administration Systems
    THE AVAILABILITY OF ORGANIC NITRATES FROM INTRAVENOUS ADMINISTRATION SYSTEMS by Paul Adrian Cossum B.Sc., M.P.S. submitted in partial fulfilment of the requirements for the degree of Master of Pharmacy UNIVERSITY OF TASMANIA - HOBART JUNE 1981 SUMMARY Nitroglycerin aind isosorbide dinitrate are two drugs which are infused intravenously during the treatment of ischaemic heart disease. The availability of these two drugs in solutions infused from plastic infusion bags or glass infusion bottles through plastic giving sets has been investigated. During simulated infusions the concentration of nitroglycerin and isosorbide dinitrate appearing in the effluent of the • giving set tubing was found to be much less than the concentration of the drug solution initially contained in the plastic infusion bag or glass infusion bottle. It was found that each component of the plastic infusion equipment sorbed the drugs to a significant extent and that the rate of disappearance of drugs from solutions stored in each component was in the rank order: giving set tubing > giving set burette > plastic infusion bag. There was no significant loss of either drug from solutions stored in glass bottles. The influence of formulation factors and storage conditions on the sorption of nitroglycerin, isosorbide dinitrate and another organic nitrate compound., ethylene glycol dinitrate, by plastic infusion equipment was studied. The extent of loss during simulated infusions was also found to be dependent on flow rate of drug solution through the giving set. The sorption of nitroglycerin and isosorbide dinitrate has clinical and pharmacokinetic significance. Losses of nitroglycerin and isosorbide dinitrate associated with their infusion through plastic Lnfusion equipment were minimised by infusing drug solutions from a glass syringe through high density polyethylene tubing.
    [Show full text]
  • Nitric Oxide Signaling in Plants
    plants Editorial Nitric Oxide Signaling in Plants John T. Hancock Department of Applied Sciences, University of the West of England, Bristol BS16 1QY, UK; [email protected]; Tel.: +44-(0)117-328-2475 Received: 3 November 2020; Accepted: 10 November 2020; Published: 12 November 2020 Abstract: Nitric oxide (NO) is an integral part of cell signaling mechanisms in animals and plants. In plants, its enzymatic generation is still controversial. Evidence points to nitrate reductase being important, but the presence of a nitric oxide synthase-like enzyme is still contested. Regardless, NO has been shown to mediate many developmental stages in plants, and to be involved in a range of physiological responses, from stress management to stomatal aperture closure. Downstream from its generation are alterations of the actions of many cell signaling components, with post-translational modifications of proteins often being key. Here, a collection of papers embraces the differing aspects of NO metabolism in plants. Keywords: nitrate reductase; nitration; nitric oxide; reactive oxygen species; stress responses; S-nitrosation; S-nitrosylation; SNO-reductase; thiol modification 1. Introduction Nitric oxide (NO) is now well acknowledged as an instrumental signaling molecule in both plants and animals [1]. First recognized as important as a signal in the control of vascular tone [2], its role in plants came to prominence in the late 1990s [3–5]. The forty years of research into NO in plants has just been highlighted by a review by Kolbert et al. [6]. In plants, NO has been found to be involved in a wide range of developmental stages and physiological responses.
    [Show full text]
  • The Noncanonical Pathway for in Vivo Nitric Oxide Generation: the Nitrate-Nitrite-Nitric Oxide Pathway
    1521-0081/72/3/692–766$35.00 https://doi.org/10.1124/pr.120.019240 PHARMACOLOGICAL REVIEWS Pharmacol Rev 72:692–766, July 2020 Copyright © 2020 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. ASSOCIATE EDITOR: CHRISTOPHER J. GARLAND The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway V. Kapil, R. S. Khambata, D. A. Jones, K. Rathod, C. Primus, G. Massimo, J. M. Fukuto, and A. Ahluwalia William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, United Kingdom (V.K., R.S.K., D.A.J., K.R., C.P., G.M., A.A.) and Department of Chemistry, Sonoma State University, Rohnert Park, California (J.M.F.) Abstract ...................................................................................694 Significance Statement. ..................................................................694 I. Introduction . ..............................................................................694 A. Chemistry of ·NO and Its Metabolism to Nitrite and Nitrate . .........................695 II. Inorganic Nitrite and Nitrate . ............................................................697 A. Historical Uses of Inorganic Nitrite.....................................................697 B. Historical Uses of Inorganic Nitrate ....................................................698 III. Sources and Pharmacokinetics of Nitrate . ................................................698
    [Show full text]
  • Dietary Nitrates, Nitrites, and Food Safety: Risks Versus Benefits
    Acta Scientific NUTRITIONAL HEALTH (ISSN:2582-1423) Volume 5 Issue 6 June 2021 Review Article Dietary Nitrates, Nitrites, and Food Safety: Risks Versus Benefits Keith R Martin* Received: April 08, 2021 Center for Nutraceutical and Dietary Supplement Research, College of Health Sci- Published: May 26, 2021 ences, University of Memphis, Memphis, USA © All rights are reserved by Keith R Martin. *Corresponding Author: Keith R Martin, Center for Nutraceutical and Dietary Supplement Research, College of Health Sciences, University of Memphis, Memphis, USA. Abstract Nitrates, as a result, are intermediates in the movement of atmospheric nitrogen into the food chain with rich dietary sources includ- Atmospheric nitrogen, via the environmental nitrogen cycle, is captured, or fixed, by symbiotic bacteria interacting with plants. ing red spinach, beetroot, etc. Nitrate-rich fertilizers may further increase nitrogen content of plants. Other sources include potable water, dietary supplements and food additives. Although prevalent in the diet, nitrates have been viewed negatively because they chemically form carcinogenic nitrosamines in acidic environments, e.g. stomach, purportedly leading to gastric cancer as well as neoplasia of the intestine, brain, pancreas, and contributing to Non-Hodgkin’s lymphoma. Other reports indicate associations with hyperthyroidism and diabetes mellitus. A second major concern with dietary nitrate consumption is the development of methemo- - globinemia particularly in infants caused by increases in methemoglobin where
    [Show full text]
  • ATSDR Case Studies in Environmental Medicine Nitrate/Nitrite Toxicity
    ATSDR Case Studies in Environmental Medicine Nitrate/Nitrite Toxicity Agency for Toxic Substances and Disease Registry Case Studies in Environmental Medicine (CSEM) Nitrate/Nitrite Toxicity Course: WB2342 CE Original Date: December 5, 2013 CE Renewal Date: December 5, 2015 CE Expiration Date: December 5, 2017 Key • Nitrate toxicity is a preventable cause of Concepts methemoglobinemia. • Infants younger than 4 months of age are at particular risk of nitrate toxicity from contaminated well water. • The widespread use of nitrate fertilizers increases the risk of well-water contamination in rural areas. About This and This educational case study document is one in a series of Other Case self-instructional modules designed to increase the Studies in primary care provider’s knowledge of hazardous Environmental substances in the environment and to promote the Medicine adoption of medical practices that aid in the evaluation and care of potentially exposed patients. The complete series of Case Studies in Environmental Medicine is located on the ATSDR Web site at URL: http://www.atsdr.cdc.gov/csem/csem.html In addition, the downloadable PDF version of this educational series and other environmental medicine materials provides content in an electronic, printable format. Acknowledgements We gratefully acknowledge the work of the medical writers, editors, and reviewers in producing this educational resource. Contributors to this version of the Case Study in Environmental Medicine are listed below. Please Note: Each content expert for this case study has indicated that there is no conflict of interest that would bias the case study content. CDC/ATSDR Author(s): Kim Gehle MD, MPH CDC/ATSDR Planners: Charlton Coles, Ph.D.; Kimberly Gehle, MD; Sharon L.
    [Show full text]
  • Analysis of Nitrogen Utilization Capability During the Proliferation and Maturation Phases of Norway Spruce (Picea Abies (L.) H.Karst.) Somatic Embryogenesis
    Article Analysis of Nitrogen Utilization Capability during the Proliferation and Maturation Phases of Norway Spruce (Picea abies (L.) H.Karst.) Somatic Embryogenesis Julia Dahrendorf 1, David Clapham 2 and Ulrika Egertsdotter 1,3,* 1 Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, SE-901 83 Umeå, Sweden; [email protected] 2 BioCentre, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden; [email protected] 3 G.W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA * Correspondence: [email protected]; Tel.: +1-404-663-6950 Received: 1 April 2018; Accepted: 22 May 2018; Published: 24 May 2018 Abstract: Somatic embryogenesis (SE) is a laboratory-based method that allows for cost-effective production of large numbers of clonal copies of plants, of particular interest for conifers where other clonal propagation methods are mostly unavailable. In this study, the effect of L-glutamine as an organic nitrogen source was evaluated for three contrasted media (containing NH4 + NO3 without glutamine, or glutamine + NO3, or glutamine without inorganic nitrogen) during proliferation and maturation of Norway spruce somatic embryos through analyses of activities of the key enzymes of nitrogen metabolism: nitrate reductase (NR), glutamine synthetase (GS) and arginase. A major change in nitrogen metabolism was indicated by the increased activity of GS from zero in the proliferation stage through maturation to high activity in somatic embryo-derived plantlets; furthermore, NR activity increased from zero at the proliferation stage to high activity in maturing embryos and somatic-embryo derived plantlets.
    [Show full text]
  • Inhibitory Effects of Sildenafil and Tadalafil on Inflammation, Oxidative
    Pharmacological Reports 71 (2019) 517–521 Contents lists available at ScienceDirect Pharmacological Reports journal homepage: www.elsevier.com/locate/pharep Original article Inhibitory effects of sildenafil and tadalafil on inflammation, oxidative stress and nitrosative stress in animal model of bronchial asthma a a, a b b Vijaya Laxmi , Rachna Gupta *, Swapan K. Bhattacharya , Arunabha Ray , Kavita Gulati a Department of Pharmacology, University College of Medical Sciences and GTB Hospital, New Delhi, India b Vallabhbhai Patel Chest Institute, New Delhi, India A R T I C L E I N F O A B S T R A C T Article history: Background: Cyclic neucleotides are involved in many cellular functions including smooth muscle Received 9 June 2018 relaxation, inflammation, and signal transduction. Sildenafil and tadalafil are phosphodiesterase-5 Received in revised form 22 January 2019 0 0 (PDE-5) inhibitors which prevent the degradation of cyclic neucleotide i.e. guanosine 3 ,5 cyclic Accepted 14 February 2019 monophosphate (cGMP) and increase the levels of cGMP. In this study sildenafil and tadalafil were Available online 15 February 2019 evaluated for their anti-inflammatory, anti-oxidative and anti-nitrosative stress potential in animal model of bronchial asthma. Keywords: Methods: Wistar rats were sensitized with 10 mg intraperitoneal (ip) ovalbumin adsorbed to 10 mg of Bronchial asthma aluminum hydroxide on day 0. Animals were given sildenafil (1 and 3 mg/kg ip) and tadalafil (1 and Inflammation 3 mg/kg ip) from day 1 to day 14. Also, on day 14 animals were challenged with ovalbumin (1 mg ip). After Oxidative stress Ovalbumin 24 h, samples were collected to analyze interleukin-4 (IL-4) and tumour necrosis factor-α (TNF-α), in Sildenafil serum and bronchoalveolar lavage fluid (BALF).
    [Show full text]
  • Possible Modes of Cytotoxicity of High Energy Aliphatic Nitroesters and N-Nitramines for Mouse Splenocytes
    CHEMIJA. 2012. Vol. 23. No. 2. P. 141–146 © Lietuvos mokslų akademija, 2012 Possible modes of cytotoxicity of high energy aliphatic nitroesters and N-nitramines for mouse splenocytes Valė Miliukienė, In this work, we report for the first time the cytotoxicity data of a large number of struc- turally diverse high energy aliphatic nitrate esters and N-nitramines (n = 20) to mouse Jonas Šarlauskas, splenocyte cells. Their concentrations causing 50% cell death (cL50) vary from 18 µM (N-nitro-diethanolamine dinitrate) to >250 µM (octahydro-1,3,5,7-tetranitro-1,3,5,7- Kastis Krikštopaitis, tetrazocine, ethylene glycol dinitrate). The log cL50 of compounds does not depend on the calculated heats of their hydride adduct formation, or voltammetric reduction peak poten- Algirdas Šaikūnas, tials, or lipophilicity. The cytotoxicity of compounds is not oxidative stress-dependent. On the other hand, their cytotoxicity is partly decreased by an inhibitor of aldehyde dehydro- Narimantas Čėnas* genase (EC 1.2.1.10), tetraethylthiuram disulfide. It shows an involvement of this enzyme in bioreductive activation of nitrate esters and N-nitramines with the liberation of nitrite, Institute of Biochemistry which is further converted to NO. of Vilnius University, Mokslininkų 12, Key words: organic nitrate ester, N-nitramine, cytotoxicity, aldehyde dehydrogenase LT-08662 Vilnius, Lithuania Abbreviations: cL50 – compound concentration causing 50% cell death, ∆Hf – heat of for- mation, Ep(7) – voltammetric reduction peak potential at pH 7.0, P – octanol / water partition coefficient, GTN – glycerol trinitrate, PETN – pentaerythritol tetranitrate, RDX – hexahy- dro-1,3,5-trinitro-1,3,5-triazine, HMX – octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine, TNT – 2,4,6-trinitrotoluene, P-450R – NADPH: cytochrome P-450 reductase, ADH – alde- hyde dehydrogenase.
    [Show full text]
  • The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins
    antioxidants Article The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins Ahmed Ismaeel 1, Evlampia Papoutsi 1, Dimitrios Miserlis 2 , Ramon Lavado 3 , Gleb Haynatzki 4, George P. Casale 5, William T. Bohannon 6, Robert S. Smith 6, Jack Leigh Eidson 6, Robert Brumberg 7, Aaron Hayson 7, Jeffrey S. Kirk 8, Carlos Castro 8, Ian Sawicki 6, Charalambos Konstantinou 9 , Luke P. Brewster 10, Iraklis I. Pipinos 5,11 and Panagiotis Koutakis 1,* 1 Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32304, USA; [email protected] (A.I.); [email protected] (E.P.) 2 Department of Surgery, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA; [email protected] 3 Department of Environmental Science, Baylor University, Waco, TX 76798, USA; [email protected] 4 Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE 68198, USA; [email protected] 5 Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA; [email protected] (G.P.C.); [email protected] (I.I.P.) 6 Department of Surgery, Baylor Scott & White Medical Center, Temple, TX 76508, USA; [email protected] (W.T.B.); [email protected] (R.S.S.); [email protected] (J.L.E.); [email protected] (I.S.) 7 Vascular Surgery Associates, Tallahassee, FL 32308, USA; rbrumberg@vsafl.com (R.B.); [email protected] (A.H.) 8 Department of Vascular Surgery, Capital Regional Medical Center, Tallahassee, FL 32308,
    [Show full text]
  • Development of Chromatography and Mass Spectrometry Methods for Explosives
    DEVELOPMENT OF CHROMATOGRAPHY AND MASS SPECTROMETRY METHODS FOR EXPLOSIVES ANALYSIS A dissertation presented to the faculty of the College of Arts and Sciences of Ohio University In partial fulfillment of the requirements for the degree Doctor of Philosophy John A. Mathis March 2004 This dissertation entitled DEVELOPMENT OF CHROMATOGRAPHY AND MASS SPECTROMETRY METHODS FOR EXPLOSIVES ANALYSIS BY JOHN A. MATHIS has been approved for the Department of Chemistry and Biochemistry and the College of Arts and Sciences by Bruce R. McCord Associate Professor of Chemistry Leslie A. Flemming Dean, College of Arts and Sciences MATHIS, JOHN A. Ph.D. March 2004. Analytical Chemistry. Development of Chromatography and Mass Spectrometry Methods for Explosives Analysis. (199 pp.) Director of Dissertation: Bruce R. McCord Novel methods for the analysis of explosives and related compounds were developed in this research. A gradient reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESIMS) method was used in the positive ion mode for the analysis of the organic additives in smokeless powders. Gas chromatography (GC) methods with electron capture detection (ECD) and negative chemical ionization mass spectrometry (MS) were developed for the separation and detection of common high explosives. Negative ion ESIMS was used for the detection of high explosive adducts. An isocratic HPLC-ESIMS method was evaluated for the simultaneous analysis of high explosives using the negative ion mode. Smokeless powders are used as propellants for small arms ammunition but have also been used as the energetic material in improvised explosive devices such as pipe bombs. Smokeless powders contain organic additives that facilitate production procedures, prevent degradation, and enhance energetic efficiency.
    [Show full text]
  • Dietary Inorganic Nitrate Reverses Features of Metabolic Syndrome in Endothelial Nitric Oxide Synthase-Deficient Mice
    Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice Mattias Carlströma,b, Filip J. Larsena, Thomas Nyströmc, Michael Hezela, Sara Borniquela, Eddie Weitzberga,1,2, and Jon O. Lundberga,1,2 aDepartment of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden; bDepartment of Medical Cell Biology, Division of Integrative Physiology, Uppsala University, SE-75123 Uppsala, Sweden; and cDepartment of Clinical Science and Education, Division of Internal Medicine, Unit for Diabetes Research, Karolinska Institutet, Södersjukhuset, SE-118 83 Stockholm, Sweden Edited* by Louis J. Ignarro, University of California Los Angeles School of Medicine, Los Angeles, CA, and approved September 7, 2010 (received for review June 23, 2010) The metabolic syndrome is a clustering of risk factors of metabolic intermediate (16, 18) and this more reactive compound is further origin that increase the risk for cardiovascular disease and type 2 metabolized to NO, nitrosothiols, and other bioactive nitrogen diabetes. A proposed central event in metabolic syndrome is a de- oxides via numerous enzymatic and nonenzymatic pathways in crease in the amount of bioavailable nitric oxide (NO) from endothe- blood and tissues (10). Interestingly, our everyday diet represents lial NO synthase (eNOS). Recently, an alternative pathway for NO a major source of inorganic nitrate, and vegetables are particularly formation in mammals was described where inorganic nitrate, rich in this anion. It has been speculated (10, 11) that the high a supposedly inert NO oxidation product and unwanted dietary nitrate content in vegetables contributes to the well-known car- constituent, is serially reduced to nitrite and then NO and other dioprotective effects of this food group.
    [Show full text]