16,16-Dimethyl prostaglandin E2 protects gastric mucosal surface epithelial cells from indomethacin-induced damage in rats.
The protective effect of 16,16-dimethyl prostaglandin E2 (dmPGE2) against early damage induced by indomethacin in the rat gastric mucosal surface epithelial cells was studied using a scanning electron microscope. Indomethacin (10 or 25 mg/kg, p.o.) induced a widespread exfoliation of the surface epithelial cells and an exposure of the lamina propria both in the corpus and antrum within 1 hr after the administration. Pretreatment with dmPGE2 (0.3, 3 or 30 micrograms/kg, p.o.) 30 min before indomethacin (25 mg/kg) dose-dependently inhibited these damages. The effects of dmPGE2, at least on the surface epithelial cells in the corpus, appear to be related to the prevention of damage formation itself and is unrelated to the enhancement of reconstitution of once damaged mucosa. Enhanced gastric motility by indomethacin was potently inhibited by pretreatment with 3 and 30 micrograms/kg of dmPGE2, but not with 0.3 micrograms/kg. dmPGE2 pretreatment (30 micrograms/kg) significantly decreased the absorption of indomethacin (25 mg/kg) when determined 10 min after giving indomethacin, but did not affect it when determined 30 and 60 min later. We conclude that dmPGE2 protects gastric mucosal surface epithelial cells from indomethacin injury at an early stage, partly by inhibiting gastric motility.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects; D007213:Indomethacin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D007408:Intestinal Absorption; D008297:Male; D008855:Microscopy, Electron, Scanning; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000897:Anti-Ulcer Agents; D011459:Prostaglandins E, Synthetic; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin