Comparative gastrointestinal toxicity of selective cyclooxygenase (COX-2) inhibitors.
Cyclooxygenase (COX-2) inhibitors were developed with the hope that they will cause fewer gastrointestinal adverse effects. Ability of selective as well as nonselective COX inhibitors to alter ischemia-reperfusion induced damage of gastric mucosa and hapten-induced colitis in rats has been compared. Celecoxib (10, 20 and 40 mg/kg(-l)) was significantly more potent at aggravating ischemia-reperfusion injury as compared to nimesulide. Similarly, celecoxib was found to maximally potentiate TNBS-induced colitis, followed by nimesulide and indomethacin. Celecoxib at its highest dose produced maximum deep histological injury. This paradoxic ulcer and colitis aggravating effect of selective COX-2 inhibitors may be explained by suppression of protective prostaglandins generated as a consequence of COX-2 induction in inflammatory states.
Shafiq
N
N
Department of Pharmacology, PGIMER, Chandigarh, India.
Malhotra
S
S
Pandhi
P
P
Nada
R
R
D000818:Animals; D000068579:Celecoxib; D003092:Colitis / Q000209:etiology / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000293:injuries; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000473:pathology; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D011720:Pyrazoles / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology; D013449:Sulfonamides / Q000633:toxicity
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; C012655:nimesulide; D007213:Indomethacin