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 were investigated. NC-1300-O-3 at doses of 3 and 10 mg/kg, p.o. significantly prevented the formation of gastric lesions by HCl.ethanol in rats, and its efficacy was not influenced by repeated administration for up to 4 weeks. The interaction between NC-1300-O-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-O-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-O-3 is an action on the gastric mucosa independent of its antisecretory effect. The cytoprotective effect of NC-1300-O-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-O-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 necrotizing agents. Moreover, NC-1300-O-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 cytoprotective effect of NC-1300-O-3.
Matsukura
H
H
Research Laboratories, Nippon Chemiphar Co., Ltd., Saitama, Japan.
Masuda
M
M
Kawaguchi
K
K
Uchida
A
A
Kamishiro
T
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin; D001562:Benzimidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006595:Hexosamines / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D006595:Hexosamines; C048733:2-((2-dimethylaminobenzyl)sulfinyl)benzimidazole; D000431:Ethanol; D005978:Glutathione; D009853:Omeprazole; D001241:Aspirin