H Ischiropoulos, I Mendiguren, D Fisher, AB Fisher and SR Thom
Institute for Environmental Medicine, University of Pennsylvania, School of Medicine, Philadelphia 19104-6068.

We examined potential mechanisms responsible for the parenchymal lung injury seen in an animal model of smoke inhalation with concurrent inflammation. Rats injected with sterile glycogen and exposed to smoke generated by the nonflaming pyrolysis of combined Douglas fir wood and polyvinylchloride showed a 74% increase in 125I-albumin lung permeability and a fivefold increase in lung myeloperoxidase (MPO) compared with control rats. There was also a significant increase in plasma indices of oxidative injury in these animals. Compared with control animals, plasma concentrations of thiobarbituric acid reactive substances (TBARS) were elevated by 62%, the concentrations of reduced sulfhydryl groups declined by 37%, and the levels of dinitrophenylhydrazine-reactive proteins (DNPH-RP) were doubled. In addition, the plasma concentrations of nitrate (NO3-) in rats exposed to glycogen plus smoke were increased three times that of control animals. Injection of the nitric oxide synthase inhibitor, NG-nitro-L- arginine methyl ester (L-NAME), immediately after smoke exposure or induction of neutropenia using either nitrogen mustard or antineutrophil antiserum, abolished the increase in concentrations of circulating NO3-, and prevented changes in plasma concentrations of TBARS, DNPH-RP, lung MPO activity, and tissue permeability index. These data suggest that neutrophil activation and the production of nitric oxide-derived oxidants contribute to the lung and plasma indices of oxidative injury in this smoke inhalation model.

This article has been cited by other articles:

				L. C Cancio Current concepts in the pathophysiology and treatment of inhalation injury Trauma, January 1, 2005; 7(1): 19 - 35. [Abstract] [PDF]

				P. Enkhbaatar, K. Murakami, K. Shimoda, A. Mizutani, R. McGuire, F. Schmalstieg, R. Cox, H. Hawkins, J. Jodoin, S. Lee, et al. Inhibition of neuronal nitric oxide synthase by 7-nitroindazole attenuates acute lung injury in an ovine model Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R366 - R372. [Abstract] [Full Text] [PDF]

				L. Fakhrzadeh, J. D. Laskin, and D. L. Laskin Deficiency in Inducible Nitric Oxide Synthase Protects Mice from Ozone-Induced Lung Inflammation and Tissue Injury Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 413 - 419. [Abstract] [Full Text] [PDF]

				M. Pelletier, C. J. Roberge, M. Gauthier, K. Vandal, P. A. Tessier, and D. Girard Activation of human neutrophils in vitro and dieldrin-induced neutrophilic inflammation in vivo J. Leukoc. Biol., September 1, 2001; 70(3): 367 - 373. [Abstract] [Full Text] [PDF]

				M. LAFFON, J.-F. PITTET, K. MODELSKA, M. A. MATTHAY, and D. M. YOUNG Interleukin-8 Mediates Injury from Smoke Inhalation to both the Lung Endothelial and the Alveolar Epithelial Barriers in Rabbits Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1443 - 1449. [Abstract] [Full Text]

				X. Y. LI, K. DONALDSON, and W. MACNEE Lipopolysaccharide-induced Alveolar Epithelial Permeability . The Role of Nitric Oxide Am. J. Respir. Crit. Care Med., April 1, 1998; 157(4): 1027 - 1033. [Abstract] [Full Text] [PDF]

				F. Hinder, M. Booke, L. D. Traber, and D. L. Traber Nitric oxide and endothelial permeability J Appl Physiol, December 1, 1997; 83(6): 1941 - 1946. [Abstract] [Full Text] [PDF]

				S. R. Thom, M. Kang, D. Fisher, and H. Ischiropoulos Release of glutathione from erythrocytes and other markers of oxidative stress in carbon monoxide poisoning J Appl Physiol, May 1, 1997; 82(5): 1424 - 1432. [Abstract] [Full Text] [PDF]

				F. HINDER, J. MEYER, M. BOOKE, J. S. EHARDT, J. R. SALSBURY, L. D. TRABER, and D. L. TRABER Endogenous Nitric Oxide and the Pulmonary Microvasculature in Healthy Sheep and during Systemic Inflammation Am. J. Respir. Crit. Care Med., May 1, 1997; 157(5): 1542 - 1549. [Abstract] [Full Text]