Mercaptoethylguanidine Inhibits the Inflammatory Response in a Murine Model of Chronic Infection with Pseudomonas aeruginosa

作者: Joseph A. Kitzmiller , Garry J. Southan , Robert W. Wilmott , Csaba Szabó , Andrew L. Salzman

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摘要: Chronic airway inflammation induced by Pseudomonas aeruginosa is the eventual cause of respiratory failure in most people affected cystic fibrosis. Recent evidence implicates involvement free radical and oxidant stress pathogenesis inflammatory injury. Here we report efficacy a novel experimental therapeutic, mercaptoethylguanidine (MEG), which has combined actions as selective inhibitor inducible nitric oxide synthase scavenger peroxynitrite, potent formed reaction superoxide radical. pulmonary infection was established FVB/N mice intratracheal administration 105 colony-forming units P. agar beads. Treatment with MEG (10 mg/kg/dose every 8 h i.p.) inhibited weight loss first 3 days reduced histologic injury at postinfection. also myeloperoxidase activity, marker neutrophil infiltration, concentrations proinflammatory cytokines interleukin-1β, tumor necrosis factor-α, macrophage protein 2 whole lung homogenates. MEG-treated animals controls had similar perioperative mortality comparable colony counts days, indicating that did not exacerbate infection. Our data suggest may be an effective immunomodulatory therapy chronic

参考文章(32)
Csaba Szabó, Andrew L. Salzman, The Physiology and Pathophysiology of Nitric Oxide in the Lung Birkhäuser Basel. pp. 279- 310 ,(1997) , 10.1007/978-3-0348-8960-5_12
Melvin Berger, Inflammation in the lung in cystic fibrosis Clinical Reviews in Allergy. ,vol. 9, pp. 119- 142 ,(1991) , 10.1007/BF02914538
S. L. Kunkel, R. M. Strieter, D. T. Nguyen, D. G. Remick, C. L. Raiford, M. A. Genord, M. K. Eskandari, Role of tumor necrosis factor-α in lipopolysaccharide-induced pathologic alterations American Journal of Pathology. ,vol. 136, pp. 49- 60 ,(1990)
H. A. Cash, B. McCullough, D. E. Woods, W. G. Johanson, J. A. Bass, A rat model of chronic respiratory infection with Pseudomonas aeruginosa. The American review of respiratory disease. ,vol. 119, pp. 453- 459 ,(2015) , 10.1164/ARRD.1979.119.3.453
Johanna M Rommens, Michael C Iannuzzi, Bat-sheva Kerem, Mitchell L Drumm, Georg Melmer, Michael Dean, Richard Rozmahel, Jeffery L Cole, Dara Kennedy, Noriko Hidaka, Martha Zsiga, Manuel Buchwald, Lap-Chee Tsui, John R Riordan, Francis S Collins, Identification of the cystic fibrosis gene: chromosome walking and jumping Science. ,vol. 245, pp. 1059- 1065 ,(1989) , 10.1126/SCIENCE.2772657
C. Szabo, L. Virag, S. Cuzzocrea, G. S. Scott, P. Hake, M. P. O'Connor, B. Zingarelli, A. Salzman, E. Kun, Protection against peroxynitrite-induced fibroblast injury and arthritis development by inhibition of poly(ADP-ribose) synthase. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 95, pp. 3867- 3872 ,(1998) , 10.1073/PNAS.95.7.3867
Michael Yeadon, Robert Price, Induction of calcium-independent nitric oxide synthase by allergen challenge in sensitized rat lung in vivo British Journal of Pharmacology. ,vol. 116, pp. 2545- 2546 ,(1995) , 10.1111/J.1476-5381.1995.TB17204.X