The effects of cyclo-oxygenase inhibitors on bile-injured and normal equine colon.
A potential adverse effect of cyclo-oxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]) in horses is colitis. In addition, we have previously shown an important role for COX-produced prostanoids in recovery of ischaemic-injured equine jejunum. It was hypothesised that the nonselective COX inhibitor flunixin would retard repair of bile-injured colon by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac would not inhibit repair as a result of continued COX-1 activity. Segments of the pelvic flexure were exposed to 1.5 mmol/l deoxycholate for 30 min, after which they were recovered for 4 h in Ussing chambers. Contrary to the proposed hypothesis, recovery of bile-injured colonic mucosa was not affected by flunixin or etodolac, despite significantly depressed prostanoid production. However, treatment of control tissue with flunixin led to increases in mucosal permeability, whereas treatment with etodolac had no significant effect. Therefore, although recovery from bile-induced colonic injury maybe independent of COX-elaborated prostanoids, treatment of control tissues with nonselective COX inhibitors may lead to marked increases in permeability. Alternatively, selective inhibition of COX-2 may reduce the incidence of adverse effects in horses requiring NSAID therapy.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D003002:Clonixin / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D003092:Colitis / Q000139:chemically induced / Q000662:veterinary; D003106:Colon / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D003840:Deoxycholic Acid / Q000009:adverse effects; D017308:Etodolac / Q000008:administration & dosage / Q000009:adverse effects*; D006734:Horse Diseases / Q000139:chemically induced; D006736:Horses; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D010539:Permeability; D011448:Prostaglandin Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D003840:Deoxycholic Acid; D017308:Etodolac; C014557:flunixin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D003002:Clonixin