16,16-Dimethyl prostaglandin E2 reduced chenodeoxycholate-induced small intestinal mucosal injury in the rat

To determine whether prostaglandin may protect the small intestinal mucosa against bile acid-induced injury, we perfused in vivo rat jejunal segments with 5 mmol/L chenodeoxycholate with and without topical pretreatment with 2.6 mumol/L (1 microgram/ml) 16,16-dimethyl prostaglandin E2. Mucosal injury by chenodeoxycholate and its time sequence was assessed by using mannitol absorption and quantitative histology after 5, 15, 30, and 45 minutes of chenodeoxycholate perfusion. Forty-five-minute perfusion with chenodeoxycholate increased mannitol absorption from 0 to 0.9 nmol/min/cm, whereas prostaglandin pretreatment reduced this increase threefold (P less than 0.001). The increase in mannitol absorption coincided with progressive denudation of epithelial cells from intestinal villi. After 45 minutes exposure to chenodeoxycholate, an average of 50 micron of the cross-sectional surface of the villi tips was denuded of epithelial cells compared with only 25 micron denuded with prostaglandin pretreatment (P less than 0.01). These data indicate that topical administration of 16,16-dimethyl prostaglandin E2 reduces both the functional and morphologic small intestinal mucosal injury caused by chenodeoxycholate.