Celecoxib, a selective cyclo-oxygenase-2 inhibitor reduces the severity ofexperimental colitis induced by dinitrobenzene sulfonic acid in rats

Inflammatory bowel disease is characterised by oxidative and nitrosative, s tress, leukocyte infiltration, upregulation of the expression of intercellu lar adhesion molecule 1 (ICAM-1) and upregulation of P-selectin in the colo n. Here, we investigate the effects of the selective cyclo-oxygenase-2 inhi bitor, celecoxib, in rats subjected to experimental colitis. Colitis was in duced in rats by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Rats experienced hemorrhagic diarrhoea and weight loss. At 4 days a fter administration of DNBS, the mucosa of the colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology, as well as a n increase in myeloperoxidase activity in the mucosa) was associated with u pregulation of ICAM-1 and P-selectin, as well as high tissue levels of malo ndialdehyde. Immunohistochemistry for nitrotyrosine and poly(ADP-ribose) po lymerase showed intense staining in the inflamed colon. Celecoxib (5 mg/kg twice a day orally) significantly reduced the degree of hemorrhagic diarrho ea and the weight loss caused by administration of DNBS. Celecoxib also cau sed a substantial reduction of (i) the degree of colonic injury, (ii) the r ise in myeloperoxidase activity (mucosa), (iii) the increase in the tissue levels of malondialdehyde, (iv) the increase in staining (immunohistochemis try) for nitrotyrosine. as well as (v) the upregulation of ICAM-1 and P-sel ectin caused by DNBS in the colon. Thus, we provide the first evidence that a selective cyclo-oxygenase-2 inhibitor celecoxib reduces the degree of co litis caused by DNBS. (C) 2001 Elsevier Science B.V. All rights reserved.