Effect of 16,16-dimethyl PGE2 and indomethacin on bile acid-induced intestinal injury and restitution in rats.
Topically administered 16,16-dimethyl prostaglandin E2 reduced bile acid-induced small intestinal mucosal injury; however, the time course of restitution after such injury and whether either exogenous or endogenous prostaglandins affect this restitution are unknown. To explore these questions, mucosal injury was produced in 50 cm small intestinal segments of anesthetized male Sprague-Dawley rats perfused in vivo for 0, 5, 15, 30, or 45 minutes with buffer containing 5 mmol/L chenodeoxycholic acid, and to assess mucosal restitution, additional rats were perfused for 45 minutes with chenodeoxycholic acid followed by 15, 30, 60 or 120 minutes with chenodeoxycholate-free buffer. The above studies were then repeated in rats receiving either intraperitoneal indomethacin (10 mg/kg) or 15 minutes of preperfusion with buffer containing 1.4 mumol/L (0.5 microgram/ml) 16,16-dimethyl prostaglandin E2. Prostaglandin pretreatment reduced and indomethacin pretreatment increased significantly the morphologic (as measured by quantitative histology) and functional (as measured by mannitol and water absorption) mucosal injury caused by chenodeoxycholic acid. However, neither pretreatment had a major impact on the time course of functional or morphologic mucosal restitution, with nearly complete restitution occurring within 1 hour. Thus, although both endogenous and exogenous prostaglandins have a significant impact on bile acid-induced small intestinal mucosal injury, this effect is not caused by an acceleration of the rate of mucosal restitution.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D001834:Body Water / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000037:antagonists & inhibitors; D007213:Indomethacin / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008353:Mannitol / Q000378:metabolism; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011459:Prostaglandins E, Synthetic; D002635:Chenodeoxycholic Acid; D008353:Mannitol; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin