| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Institute of Pharmacology,
Department of Biomorphology, School of Medicine, and
Institute of General Surgery, University of Messina, Italy
1Correspondence: Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica-Policlinico Universitario Via C. Valeria-Gazzi, 98100 Messina, Italy. E-mail: salvator{at}www.unime.it
ABSTRACT
Oxidative stress has been suggested as a potential mechanism in the
pathogenesis of lung inflammation. The pharmacological profile of
n-acetylcysteine (NAC), a free radical scavenger, was
evaluated in an experimental model of lung injury (carrageenan-induced
pleurisy). Injection of carrageenan into the pleural cavity of rats
elicited an acute inflammatory response characterized by fluid
accumulation in the pleural cavity that contained many neutrophils
(PMNs), an infiltration of PMNs in lung tissues and subsequent lipid
peroxidation, and increased production of nitrite/nitrate, tumor
necrosis factor 
, and interleukin 1ß. All parameters of
inflammation were attenuated by NAC treatment. Furthermore, carrageenan
induced an up-regulation of the adhesion molecules ICAM-1 and
P-selectin, as well as nitrotyrosine and poly (ADP-ribose) synthetase
(PARS), as determined by immunohistochemical analysis of lung tissues.
The degree of staining for the ICAM-1, P-selectin, nitrotyrosine, and
PARS was reduced by NAC. In vivo NAC treatment significantly reduced
peroxynitrite formation as measured by the oxidation of the fluorescent
dihydrorhodamine-123, prevented the appearance of DNA damage, an
decrease in mitochondrial respiration, and partially restored the
cellular level of NAD+ in ex vivo macrophages harvested from the
pleural cavity of rats subjected to carrageenan-induced pleurisy. A
significant alteration in the morphology of red blood cells was
observed 24 h after carrageenan administration. NAC treatment has
the ability to significantly diminish the red blood cell alteration.
Our results clearly demonstrate that NAC treatment exerts a protective
effect and clearly indicate that NAC offers a novel therapeutic
approach for the management of lung injury where radicals have been
postulated to play a role.—Cuzzocrea, S., Mazzon, E., Dugo, L.,
Serraino, I., Ciccolo, A., Centorrino, T., De Sarro, A., Caputi,
A. P. Protective effects of n-acetylcysteine on
lung injury and red blood cell modification induced by carrageenan in
the rat.
Key Words: inflammation • nitric oxide • peroxynitrite • n-acetylcysteine • superoxide
This article has been cited by other articles:
|
|
 |
|
  S. Cuzzocrea, S. Bruscoli, E. Mazzon, C. Crisafulli, V. Donato, R. Di Paola, E. Velardi, E. Esposito, G. Nocentini, and C. Riccardi Peroxisome Proliferator-Activated Receptor-{alpha} Contributes to the Anti-Inflammatory Activity of Glucocorticoids Mol. Pharmacol., February 1, 2008; 73(2): 323 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Borthakur, S. Bhattacharyya, P. K. Dudeja, and J. K. Tobacman Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G829 - G838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cuzzocrea, S. Bruscoli, C. Crisafulli, E. Mazzon, M. Agostini, C. Muia, E. Esposito, R. Di Virgilio, R. Meli, E. Vegeto, et al. Estrogen Receptor Antagonist Fulvestrant (ICI 182,780) Inhibits the Anti-Inflammatory Effect of Glucocorticoids Mol. Pharmacol., January 1, 2007; 71(1): 132 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Rhoden, J. Lawrence, J. J. Godleski, and B. Gonzalez-Flecha N-Acetylcysteine Prevents Lung Inflammation After Short-Term Inhalation Exposure to Concentrated Ambient Particles Toxicol. Sci., June 1, 2004; 79(2): 296 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.N.R. Dekhuijzen Antioxidant properties of N-acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease Eur. Respir. J., April 1, 2004; 23(4): 629 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Blesa, J. Cortijo, M. Mata, A. Serrano, D. Closa, F. Santangelo, J.M. Estrela, J. Suchankova, and E.J. Morcillo Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen Eur. Respir. J., March 1, 2003; 21(3): 394 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bucolo, S. Cuzzocrea, E. Mazzon, and A. P. Caputi Effects of Cloricromene, a Coumarin Derivative, on Endotoxin-Induced Uveitis in Lewis Rats Invest. Ophthalmol. Vis. Sci., March 1, 2003; 44(3): 1178 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Macdonald, H. F. Galley, and N. R. Webster Oxidative stress and gene expression in sepsis Br. J. Anaesth., February 1, 2003; 90(2): 221 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cuzzocrea, N. S. Wayman, E. Mazzon, L. Dugo, R. Di Paola, I. Serraino, D. Britti, P. K. Chatterjee, A. P. Caputi, and C. Thiemermann The Cyclopentenone Prostaglandin 15-Deoxy-Delta 12,14-Prostaglandin J2 Attenuates the Development of Acute and Chronic Inflammation Mol. Pharmacol., May 1, 2002; 61(5): 997 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Silva, E. F. de Assis, L. F. C. Caiado, G. K. Marathe, M. T. Bozza, T. M. McIntyre, G. A. Zimmerman, S. M. Prescott, P. T. Bozza, and H. C. Castro-Faria-Neto Monocyte Chemoattractant Protein-1 and 5-Lipoxygenase Products Recruit Leukocytes in Response to Platelet-Activating Factor-Like Lipids in Oxidized Low-Density Lipoprotein J. Immunol., April 15, 2002; 168(8): 4112 - 4120. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
