Aggravation of inflammatory bowel disease by cyclooxygenase-2 inhibitors in rats.
The objective of the present study was to determine the effect of a selective cyclooxygenase-2 (COX-2) inhibitor in in-vivo dextran sodium sulfate (DSS)-stimulated distal colon tissues of the rat. Longitudinal colon tissue sections from DSS-treated rats exhibited noticeable inflammation, altered contraction, increased myleoperoxidase activity, and oxidative stress. When the animals were pretreated with celecoxib, a selective COX-2 inhibitor, the flare of the colon was further worsened in terms of all the parameters studied. There was a reduction in PGE2 levels on chronic administration of celecoxib in DSS-treated animals. The results of the present study suggest that COX-2 enzyme and prostaglandins derived from COX-2 might play a defensive role in protecting ulceration of the colon akin to that seen in the upper gastrointestinal tract.
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Vijay Pal
VP
Singh
Chandrashekhar S
CS
Patil
Naveen K
NK
Jain
Shrinivas K
SK
Kulkarni
D000818:Animals; D000068579:Celecoxib; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016264:Dextran Sulfate; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D016264:Dextran Sulfate; D009195:Peroxidase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D015232:Dinoprostone; D007213:Indomethacin