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ABSTRACT-The cytoprotective effect of NC-1300-0-3 and its mechanism of action were investigated.NC-1300-0-3 at doses of 3 and 10 mg/kg, p.o. significantly prevented the formation of gastric lesions by HC1 -ethanol in rats, and its efficacy was not influenced by repeated administration for up to 4 weeks. The interaction between NC-1300-0-3 and necrotizing agents in the stomach, which is considered to be related to the development of cytoprotection, was not observed. A preventive effect of NC-1300-0-3 against gastric lesions was observed at the same dose even when gastric secretion was completely inhibited by pretreatment with omeprazole. This suggests that the cytoprotective effect of NC-1300-0-3 is an action on the gastric mu cosa independent of its antisecretory effect. The cytoprotective effect of NC-1300-0-3 was not affected by pretreatment with indomethacin but was partly decreased by N-ethylmaleimide pretreatment, suggesting the participation of endogenous sulfhydryl compounds in the action of NC-1300-0-3. This compound dose dependently increased 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 surface mucus and mucosal hexosamine content caused by necrotiz ing agents. Moreover, NC-1300-0-3 at doses of 10 and 30 mg/kg, p.o. significantly inhibited the increased gastric vascular permeability caused by alcohol treatment; and at 30 mg/kg, p.o., it inhibited the reduction in potential difference caused by aspirin in rats. These actions were suggested to contribute to the cytoprotec tive effect of NC-1300-0-3.

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