Effects of prostaglandin and indomethacin on diet-induced acute pancreatitis in mice.
This study was performed to determine the effects of exogenous prostaglandin and a prostaglandin synthetase inhibitor on experimental pancreatitis in mice. An ethionine-supplemented choline-deficient diet was used to induce pancreatitis in 4-6-wk-old Swiss Webster mice. Mice were injected subcutaneously with 16,16-dimethyl prostaglandin E2 (0.1, 1.0, 10 micrograms X kg-1 X day-1), indomethacin (0.05, 0.5, 5 mg X kg-1 X day-1), or saline for 7 days. The ethionine-supplemented choline-deficient diet was introduced 24 h after the first injection, and animals ate the test diet for 48 h. A 55% mortality was observed in control animals (n = 100) treated with carrier alone. Treatment with 10 micrograms X kg-1 X day-1 of 16,16-dimethyl prostaglandin E2 significantly decreased (p less than 0.01) mortality to 12% (n = 100). Improved survival was accompanied by a significant (p less than 0.05) decrease in the pancreatic content of free chymotrypsin and a decrease in histologic damage. Treatment with 5 mg X kg-1 X day-1 of indomethacin (n = 30) significantly (p less than 0.01) increased mortality in diet-treated rats from a control rate of 55% to 100%. These studies demonstrate a protective effect of prostaglandin on the pancreas and suggest a role for endogenous prostaglandins in the pathophysiology of pancreatitis.
D015064:16,16-Dimethylprostaglandin E2 / Q000627:therapeutic use*; D000208:Acute Disease; D000818:Animals; D002918:Chymotrypsin / Q000032:analysis; D004032:Diet / Q000009:adverse effects; D005260:Female; D007213:Indomethacin / Q000009:adverse effects*; D051379:Mice; D010179:Pancreas / Q000032:analysis; D010195:Pancreatitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use*; D014357:Trypsin / Q000032:analysis; D014362:Trypsinogen / Q000032:analysis
D011459:Prostaglandins E, Synthetic; D014362:Trypsinogen; D002918:Chymotrypsin; D014357:Trypsin; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin