Anti-inflammatory effects of exogenous uridine in an animal model of lung inflammation |
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| Authors: | Evaldsson C Rydén I Uppugunduri S |
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| Affiliation: | 1. Channing Division of Network Medicine, Brigham and Women''s Hospital Harvard Medical School, Boston, MA 02115, USA;2. Division of Pediatric Allergy & Immunology, Massachusetts General Hospital for Children, Boston, MA 02114, USA;3. Division of Pulmonary Medicine, Allergy and Immunology, Children''s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA 15260, USA;1. Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico;2. Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 México, D.F., Mexico;3. Unidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Secretaría de Salud, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, 14080 México, D.F., Mexico;1. Department of Electrical and Computer Engineering, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan;2. Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan;3. ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, University of Wollongong, Wollongong, NSW 2500, Australia;4. Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan;5. Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan |
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| Abstract: | ![]()
Nucleosides like adenosine, uridine and their nucleotide derivatives (e.g. ATP and UTP) play important roles in many cellular functions, sometimes by acting as signalling molecules through binding to specific P2 nucleotide receptors. P2 receptors are subdivided into P2X and P2Y subfamilies, the latter of which are G-protein coupled receptors. P2Y receptors and nucleoside transporters have been detected in human and rat lungs, where they mediate effects of interest in airway diseases. The aim of this study was to investigate whether uridine has any anti-inflammatory properties in an asthma-like animal model of lung inflammation. The Sephadex-induced lung inflammation model in Sprague-Dawley rats was chosen mainly due to its localised inflammatory response and uridine's limited oral bioavailability. The dextran beads, with or without the addition of uridine, were instilled intratracheally into the lungs, which were excised and examined after 24 h. Sephadex alone led to massive oedema and infiltration of macrophages, neutrophils and eosinophils. Microgranulomas with giant cell formations were clearly visible around the partially degraded beads. Uridine reduced both the oedema and the infiltration of leukocytes significantly, measured as lung wet weight and leukocyte counts in bronchoalveolar lavage fluid, respectively. Uridine appeared to affect the tumour necrosis factor (TNF) levels, although this could not be statistically confirmed due to large variations within the Sephadex control group. We conclude that uridine has anti-inflammatory effects, and that the exact mechanism(s) of action requires further study. |
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