Cytoprotective Action of Mast Cell Stabilizers against Ethanol-Induced Gastric Les ons in Rats

Abstract

We examined the effects of FPL-52694 and disodium cromoglycate (DSCG), mast cell stabilizers on HCl.cntdot.ethanol-induced gastric lesions in rats and investigated the factors involved in their protection. Oral (p.o.) administration of 1 ml of HCl.cntdot.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.cntdot.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 (> 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 < 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.cntdot.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.