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

Inflamm Res. 2005 Apr;54(4):145-51. doi: 10.1007/s00011-004-1337-2.


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.

MeSH terms

  • Animals
  • Colitis / chemically induced*
  • Colitis / drug therapy*
  • Colitis / enzymology
  • Colitis / pathology
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dextran Sulfate / pharmacology*
  • Dinoprostone / metabolism
  • Immunohistochemistry
  • Lactones / pharmacology*
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Prostaglandin D2 / metabolism
  • Sulfones / pharmacology*


  • Cyclooxygenase Inhibitors
  • Lactones
  • Membrane Proteins
  • Sulfones
  • rofecoxib
  • Dextran Sulfate
  • Cyclooxygenase 1
  • Ptgs1 protein, mouse
  • Dinoprostone
  • Prostaglandin D2