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.