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  • Title: The COX-2 inhibitor, rofecoxib, ameliorates dextran sulphate sodium induced colitis in mice.
    Author: Martín AR, Villegas I, Alarcón de la Lastra C.
    Journal: Inflamm Res; 2005 Apr; 54(4):145-51. PubMed ID: 15883736.
    Abstract:
    OBJECTIVE: 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)-1beta, prostaglandin (PG)E2 and PGD2 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-1beta levels. PGE2, and PGD2 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-1beta and returning to normal COX-1 expression in the inflamed colonic mucosa.
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