The COX-2 inhibitor, rofecoxib, ameliorates dextran sulphate sodium induced colitis in mice

Objetive: We have evaluated the efficacy of the selective cyclo-oxygenase (COX)-2 inhibitor, rofecoxib, for the prevention of experimental colitis. Material and methods: To induce colitis BALB/c mice received 5% dextran sulphate sodium (DSS) in their drinking water continuously for 7 days. Rofecoxib (2.5 - 10 mg/kg body weight, p. o.) was administered throughout the treatment period with DSS. Colitis was quantified by a clinical damage score, colon length, weight loss, stool consistency and rectal bleeding. Inflammatory response was assessed by neutrophil infiltration, determined by histology and myeloperoxidase (MPO) activity. Interleukin ( IL)-1 beta, prostaglandin (PG) E-2 and PGD(2) levels in colon mucosa and the immunohistochemical expression of COX-1 and - 2 were also studied. Results: The COX-2 inhibitor ameliorated severe colitis, reduced the degree of inflammation through reduction of neutrophil infiltration and IL-1 beta levels. PGE(2), and PGD(2) synthesis were significantly reduced in DSS-treated groups. Indeed, treatment with rofecoxib diminished the lost of COX-1 caused by DSS in the crypt epithelium whereas expression of COX-2 remained unaffected. Conclusions: Rofecoxib is protective in acute DSS - induced colitis, probably by reducing neutrophil infiltration, inhibiting up-regulation of IL-1 beta and returning to normal COX-1 expression in the inflamed colonic mucosa.