Cytoprotective action of mast cell stabilizers against ethanol-induced gastric lesions in rats.
We examined the effects of FPL-52694 and disodium cromoglycate (DSCG), mast cell stabilizers, on HCl X ethanol-induced gastric lesions in rats and investigated the factors involved in their protection. Oral (p.o.) administration of 1 ml of HCl X ethanol (60% in 150 mM HCl) induced linear hemorrhagic lesions in the gastric mucosa within 1 hr. FPL-52694 (1-30 mg/kg), given both p.o. and intraperitoneally (i.p.), prevented these lesions in a dose-related manner. DSCG (3-30 mg/kg) also dose-dependently reduced the formation of these lesions when this agent was given i.p. The protective effects of these drugs on HCl X ethanol-induced lesions were significantly attenuated by pretreatment with indomethacin (5 mg/kg, s.c.). Both gastric acid secretion and transmucosal potential difference were significantly reduced by topical application of FPL-52694 (greater than 10 mg/kg), but were not affected by i.p. administration of FPL-52694 and DSCG. On the other hand, gastric motor activity measured as intraluminal pressure recordings was significantly inhibited for 2 hr by both FPL-52694 (p.o. and i.p.) and DSCG (i.p.), and these effects were also significantly antagonized with prior administration of indomethacin. A significant relationship was found between the effects of these two drugs on the lesion index and the motility index (r: 0.9214, P less than 0.01), but not other factors. These results suggest that mast cell stabilizers such as FPL-52694 and DSCG protect the gastric mucosa against HCl X ethanol through a systemic action, probably mediated with endogenous prostaglandins. Although the mechanism of cytoprotection remains unknown, this property may be related to their inhibitory effects on gastric motor activity.
D000818:Animals; D000897:Anti-Ulcer Agents; D001639:Bicarbonates / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology*; D004205:Cromolyn Sodium / Q000494:pharmacology*; D000431:Ethanol / Q000037:antagonists & inhibitors; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
D000897:Anti-Ulcer Agents; D001639:Bicarbonates; D002867:Chromones; D000431:Ethanol; C029061:FPL-52694; D004205:Cromolyn Sodium; D007213:Indomethacin