Protective effects of Celecoxib on lung injury and red blood cells modification induced by carrageenan in the rat

In the present study, we evaluated the effect of Celecoxib, a selective COX-2 inhibitor, in an acute model of lung injury induced by carrageenan administration in the rats. Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by: fluid accumulation in the pleural cavity which contained a large number of polymorphonuclear neutrophils (PMNs) as well as an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of prostaglandin E-2 (PGE(2)), tumor necrosis factor alpha (TNFalpha), and interleukin-1beta. All parameters of inflammation were attenuated by Celecoxib. Furthermore, carrageenan induced an upregulation of the adhesion molecules ICAM-I 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 Celecoxib. These results clearly confirmed that COX-2 plays a critical role in the development of the inflammatory response by altering key components of the inflammatory cascade. Therefore, selective inhibitor of COX-2 such as Celecoxib, offers a therapeutic approach for the management of various inflammatory diseases. (C) 2002 Elsevier Science Inc. All rights reserved.