title: Effects and mechanism of the selective COX-2 inhibitor, celecoxib, on rat colitis induced by trinitrobenzene sulfonic acid.
abstract: OBJECTIVE
  To investigate the action of celecoxib (a selective COX-2 inhibitor) in a rat model of colitis induced by trinitrobenzene sulfonic acid (TNBS).
  
  
  METHODS
  Rats were randomized into four groups. Colitis was induced in groups 1 and 2 by intracolonic administration of TNBS (25 mg/mL) in 50% ethanol (0.25 mL). The rats in group 1 received oral celecoxib (1.25 mg/kg) and those in group 2 received distilled water (1 mL/0.3 kg), beginning 3 h before induction of colitis and continuing twice daily thereafter for up to 7 days. The rats in group 4 received oral celecoxib (1.25 mg/kg) twice daily for 7 days and those in group 3 were healthy controls. All rats that survived 7 days were killed and both the severity of colonic mucosal damage and the prostaglandin E2 (PGE2) concentrations of the colonic mucosa were assessed.
  
  
  RESULTS
  The colonic mucosal damage scores for groups 1 and 2 were 11.15 +/- 3.30 and 8.50 +/- 2.82, respectively, both of which were significantly higher than the score for the healthy controls (0.62 +/- 0.09; P < 0.01, P < 0.01). The score of group 1 was significantly higher than that of group 2 (P < 0.05). No difference was found between the scores of groups 3 and 4. The mucosal concentrations of PGE2 in groups 1 and 2 were 12.00 +/- 4.33 pg/microg and 17.20 +/- 9.62 pg/microg, respectively, both of which were significantly higher than the concentration in the healthy controls (6.02 +/- 3.39 pg/microg; P < 0.05, both). The PGE2 concentration of group 1 was decreased significantly compared with that of group 2 (P < 0.05). No difference was found between groups 3 and 4.
  
  
  CONCLUSIONS
  The results suggest that treatment with celecoxib exacerbates inflammation-associated colonic injury in experimental colitis induced by TNBS. This preliminary study shows that the mechanism is related to suppression by the COX-2 inhibitor of the PG derived from COX-2, but further study is needed to identify if there are other related mechanisms.
authors.affiliation: Department of Gastroenterology, Third Hospital, Peking University, Beijing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Yu Min
authors.initials: YM
authors.lastname: Lu
authors.forename: Xiu Yun
authors.initials: XY
authors.lastname: Dong
mesh_terms: D000818:Animals; D000068579:Celecoxib; D003092:Colitis / Q000188:drug therapy* / Q000209:etiology / Q000662:veterinary; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis; D004195:Disease Models, Animal; D007249:Inflammation; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects / Q000633:toxicity
chemical_list: D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D014302:Trinitrobenzenesulfonic Acid; D000068579:Celecoxib; D015232:Dinoprostone