Mucosal lesions induced in the rat intestinal tract by the anti-inflammatory drug, Wy-41,770, a weak inhibitor of prostaglandin synthesis, contrasted with those from the potent prostaglandin inhibitor, indomethacin.
The intestinal ulcerogenic activity of the weak prostaglandin synthesis inhibitor drug Wy-41,770 [5H-dibenzo(a,d)-cyclohepten-5-ylidine] was contrasted with the potent synthesis inhibitor, indomethacin, in rats to establish the relationship of inhibition of prostaglandin synthesis to the intestinal damage. Wy-41,770 induced superficial erosions only in the cecum 26 hr after a single oral dose of 250 or 500 mg/kg of the drug, progressing to ulcers after 5 days dosing with ultrastructural evidence of bacteria in the mucosa. Indomethacin (5 or 10 mg/kg po) induced mucosal erosions in the ileum, initially at 26 hr progressing to ulcers after 5 days. Fewer bacteria were seen in the ileal mucosa of indomethacin-treated rats. Both drugs reduced prostaglandin E in those regions of the intestine coincident with the known accumulation of these drugs at sites of mucosal injury. Site-specific intestinal damage from these 2 drugs is associated with inhibition of the synthesis of mucosal-protective prostanoids, followed by pronounced bacterial invasion through the damage mucosae with consequent appearance of local immuno-inflammatory reactions.
D000085:Acetates / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000633:toxicity*; D001419:Bacteria / Q000472:pathogenicity; D016861:Cyclooxygenase Inhibitors; D003986:Dibenzocycloheptenes / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D007213:Indomethacin / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014456:Ulcer / Q000139:chemically induced
D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D003986:Dibenzocycloheptenes; D011453:Prostaglandins; C042276:Wy 41770; D007213:Indomethacin