Cytoprotective Effect of NC-1300-O-3 against Gastric Lesions Induced by Necrotizing Agents in Rats.

Abstract

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.

Mechanism by Which Orally Administered Leminoprazole Stimulates Mucus Synthesis in Rats

“…Our results support the previous ones of Matsukura et al [4,5] and Ishihara et al [6] that leminoprazole induces an accumu- Fig. 7.…”

“…Furthermore, leminoprazole protects the gastric mucosa against various ulcerogenic stimuli, such as ethanol, indomethacin and water-immersion restraint. The protective effect of leminprazole is considered to be through its antisecretory effect, mucus synthesis-promoting effect, and direct cytoprotec- Takahashi/Okabe tive effect on gastric epithelial cells [1,[3][4][5][6][7][8][9][10]. It was reported that accumulation of mucus glycoproteins in the gastric mucosa is observed after the oral administration of leminoprazole to rats [4][5][6].…”

“…The protective effect of leminprazole is considered to be through its antisecretory effect, mucus synthesis-promoting effect, and direct cytoprotec- Takahashi/Okabe tive effect on gastric epithelial cells [1,[3][4][5][6][7][8][9][10]. It was reported that accumulation of mucus glycoproteins in the gastric mucosa is observed after the oral administration of leminoprazole to rats [4][5][6]. In vitro studies also revealed that leminoprazole enhances mucus synthesis by rat gastric strips and rabbit gastric mucosal cells [7,8].…”

Leminoprazole Protects Cultured Gastric Mucosal Cells against Damage Caused by Ethanol, Indometacin and Taurocholate

“…Basel L l \ 0031-7012/97/0543-0118SI2.00/0 E-Mail kargcr@karger.ch F ax+ 41 61 306 12 34 http://www.kargcr.ch tory effect and partly through an unknown mechanism [1][2][3][4]. It was reported that lemi noprazole stimulates mucin biosynthesis and mucus secretion in the rat stomach [5,6].…”