H. Matsukura et al., CYTOPROTECTIVE EFFECT OF NC-1300-O-3 AGAINST GASTRIC-LESIONS INDUCED BY NECROTIZING AGENTS IN RATS, Japanese Journal of Pharmacology, 65(1), 1994, pp. 9-18
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.