CYTOPROTECTIVE EFFECT OF NC-1300-O-3 AGAINST GASTRIC-LESIONS INDUCED BY NECROTIZING AGENTS IN RATS

The cytoprotective effect of NC-1300-O-3 and its mechanism of action w ere investigated. NC-1300-O-3 at doses of 3 and 10 mg/kg, p.o. signifi cantly prevented the formation of gastric lesions by HCl.ethanol in ra ts, and its efficacy was not influenced by repeated administration for up to 4 weeks. The interaction between NC-1300-O-3 and necrotizing ag ents in the stomach, which is considered to be related to the developm ent of cytoprotection, was not observed. A preventive effect of NC-130 0-O-3 against gastric lesions was observed at the same dose even when gastric secretion was completely inhibited by pretreatment with omepra zole. This suggests that the cytoprotective effect of NC-1300-O-3 is a n action on the gastric mucosa independent of its antisecretory effect . The cytoprotective effect of NC-1300-O-3 was not affected by pretrea tment with indomethacin but was partly decreased by N-ethylmaleimide p retreatment, suggesting the participation of endogenous sulfhydryl com pounds in the action of NC-1300-O-3. This compound dose-dependently in creased the hexosamine content in the gastric lumen in rats at a dose range of 3-30 mg/kg, p.o. and slightly inhibited a reduction in surfac e mucus and mucosal hexosamine content caused by necrotizing agents. M oreover, NC-1300-O-3 at doses of 10 and 30 mg/kg, p.o. significantly i nhibited the increased gastric vascular permeability caused by alcohol treatment; and at 30 mg/kg, p.o., it inhibited the reduction in poten tial difference caused by aspirin in rats. These actions were suggeste d to contribute to the cytoprotective effect of NC-1300-O-3.