Morphological and physiological effects of a cytoprotective prostaglandin analog (rioprostil) on the rat gastric mucosa.
This study was undertaken to investigate the ability of a cytoprotective synthetic primary alcohol PGE1 analog, rioprostil, to protect the rat gastric mucosa against topically applied 40% (v/v) ethanol. Use of an ex vivo gastric chamber model facilitated correlation of changes in dynamic physiological parameters (PD and net cation fluxes) with changes in mucosal structure. We were particularly interested in defining changes in mucosal structure which accompanied topical application of rioprostil and which might explain subsequent resistance to the effects of ethanol. Topical application of rioprostil for 10 min provided concentration-dependent protection against ethanol-induced hemorrhagic erosions. The most effective dose and concentration tested (25 micrograms rioprostil at a concentration of 10 micrograms/ml) completely prevented ethanol-induced lesion formation. Protection was not accompanied by significant preservation of the interfoveolar epithelium against ethanol, but did involve prevention of vasocongestion and limitation of damage to the superficial epithelium. Complete recovery of physiological parameters indicative of gastric mucosal barrier integrity occurred within 20 min. The most effective concentrations of rioprostil produced extensive subepithelial edema and, concurrently, significant increases in net efflux of sodium ions, decreases in mucosal PD, and loss of mucosal folding.
D000287:Administration, Topical; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced; D000431:Ethanol / Q000009:adverse effects / Q000037:antagonists & inhibitors; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D008564:Membrane Potentials / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D011188:Potassium / Q000378:metabolism; D011453:Prostaglandins / Q000145:classification / Q000494:pharmacology*; D011458:Prostaglandins E / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016630:Rioprostil; D012964:Sodium / Q000378:metabolism
D000897:Anti-Ulcer Agents; D011453:Prostaglandins; D011458:Prostaglandins E; D000431:Ethanol; D016630:Rioprostil; D012964:Sodium; D011188:Potassium