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-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 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.
Cuzzocrea
Salvatore
S
Institute of Pharmacology, University of Messina, Messina, Italy. salvator@www.unime.it
Mazzon
Emanuela
E
Sautebin
Lidia
L
Dugo
Laura
L
Serraino
Ivana
I
De Sarro
Angela
A
Caputi
Achille P
AP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002351:Carrageenan; D000068579:Celecoxib; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000187:drug effects* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D010998:Pleurisy / Q000188:drug therapy*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000517:prevention & control*; D013449:Sulfonamides / Q000627:therapeutic use*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D019007:P-Selectin; D011720:Pyrazoles; D013449:Sulfonamides; D018799:Intercellular Adhesion Molecule-1; C002744:3-nitrotyrosine; D014443:Tyrosine; D002351:Carrageenan; D011065:Poly(ADP-ribose) Polymerases; D000068579:Celecoxib