title: Celecoxib, a selective cyclo-oxygenase-2 inhibitor reduces the severity of experimental colitis induced by dinitrobenzene sulfonic acid in rats.
abstract: Inflammatory bowel disease is characterised by oxidative and nitrosative stress, leukocyte infiltration, upregulation of the expression of intercellular adhesion molecule 1 (ICAM-1) and upregulation of P-selectin in the colon. Here, we investigate the effects of the selective cyclo-oxygenase-2 inhibitor, celecoxib, in rats subjected to experimental colitis. Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Rats experienced hemorrhagic diarrhoea and weight loss. At 4 days after administration of DNBS, the mucosa of the colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology, as well as an increase in myeloperoxidase activity in the mucosa) was associated with upregulation of ICAM-1 and P-selectin, as well as high tissue levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly(ADP-ribose) polymerase showed intense staining in the inflamed colon. Celecoxib (5 mg/kg twice a day orally) significantly reduced the degree of hemorrhagic diarrhoea and the weight loss caused by administration of DNBS. Celecoxib also caused a substantial reduction of (i) the degree of colonic injury, (ii) the rise in myeloperoxidase activity (mucosa), (iii) the increase in the tissue levels of malondialdehyde, (iv) the increase in staining (immunohistochemistry) for nitrotyrosine, as well as (v) the upregulation of ICAM-1 and P-selectin caused by DNBS in the colon. Thus, we provide the first evidence that a selective cyclo-oxygenase-2 inhibitor celecoxib reduces the degree of colitis caused by DNBS.
authors.affiliation: Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario Via C. Valera, Gazzi, 98100, Messina, Italy. salvator@www.unime.it
authors.forename: S
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: E
authors.initials: E
authors.lastname: Mazzon
authors.forename: I
authors.initials: I
authors.lastname: Serraino
authors.forename: L
authors.initials: L
authors.lastname: Dugo
authors.forename: T
authors.initials: T
authors.lastname: Centorrino
authors.forename: A
authors.initials: A
authors.lastname: Ciccolo
authors.forename: L
authors.initials: L
authors.lastname: Sautebin
authors.forename: A P
authors.initials: AP
authors.lastname: Caputi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001557:Benzenesulfonates; D001835:Body Weight; D000068579:Celecoxib; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007527:Isoenzymes / Q000032:analysis; D015227:Lipid Peroxidation; D008297:Male; D009504:Neutrophils / Q000276:immunology; D019007:P-Selectin / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000032:analysis; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001557:Benzenesulfonates; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007527:Isoenzymes; D019007:P-Selectin; D011720:Pyrazoles; D013449:Sulfonamides; C007488:dinitrobenzenesulfonic acid; D018799:Intercellular Adhesion Molecule-1; D030421:Peroxynitrous Acid; D009195:Peroxidase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D011065:Poly(ADP-ribose) Polymerases; D000068579:Celecoxib