The COX-2 inhibitor, rofecoxib, ameliorates dextran sulphate sodium induced colitis in mice.
OBJECTIVE
We have evaluated the efficacy of the selective cyclo-oxygenase (COX)-2 inhibitor, rofecoxib, for the prevention of experimental colitis.


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.
Martín
A R
AR
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor García González Street, 2, 41012, Seville, Spain.
Villegas
I
I
Alarcón de la Lastra
C
C
D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016264:Dextran Sulfate / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D007150:Immunohistochemistry; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015230:Prostaglandin D2 / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D016264:Dextran Sulfate; D051545:Cyclooxygenase 1; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone; D015230:Prostaglandin D2