Original Articles
Copyright ©The Author(s) 1999. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 15, 1999; 5(6): 477-482
Published online Dec 15, 1999. doi: 10.3748/wjg.v5.i6.477
Protective effect of Irsogladine on monochloramine induced gastric mucosal lesions in rats: a comparative study with rebamipide
Hedeichiro Yamamoto, M Umeda, H Mizoguchi, S Kato, K Takeuchi
Hedeichiro Yamamoto, M Umeda, H Mizoguchi, S Kato, K Takeuchi, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmace utical University, Misasagi, Yamashina, Kyoto 607-8414, Japan
Hedeichiro Yamamoto, male born on 1975-07-10 in Osaka City, Japan, graduated from Kyoto Pharmaceutical University in 1998, now a graduated student of Kyoto Pharmaceutical University, majoring in gastrointestinal pharmacolog y and physiology and having 6 papers published.
Author contributions: All authors contributed equally to the work.
Correspondence to: Shinichi Kato, Ph.D., Department of Pharmacol ogy and Experimental Therapeutics, Kyoto Pharmaceutical Unviersity, Misasagi, Ya mashina, Kyoto 607-8414, Japan. skato@mb.kyoto-phu.ac.jp
Telephone: +81-75-595-4680 Fax: +81-75-595-4774
Received: August 31, 1999
Revised: September 20, 1999
Accepted: October 14, 1999
Published online: December 15, 1999

AIM: To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine ( NH2Cl ) in rat stom ach, in comparison with rebamipide, another antiulcer drug with cytoprotective activity.

METHODS AND RESULTS: Oral administration of NH2Cl (120 mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs. Both irso gladine (1 mg/kg-10 mg/kg, po) and rebamipide (30 mg/kg-100 mg/kg, po) dose-dependently prevented the development of these lesions in response to NH2Cl, the effect of irsogladine was significant at 3 mg/kg or greater, and that of rebamipide only at 100 mg/kg. The protective effect of irsogladine on NH2Cl-induced gastric lesions was significantly reduced by NG-nitro-L-arginine methyl ester (L-NAME) but not by indomethacin, while that of rebamipide was significantly mitigated by indom ethacin but not by L-NAME. Topical application of NH2Cl (20mM) caused a marked reduction of potential difference (PD) in ex-vivo stomachs. This PD reduction was not affected by mucosal application of irsogladine, but significa ntly prevented by rebamipide. The mucosal exposure to NH4OH (120 mM) also caused a marked PD reduction in the ischemic stomach (bleeding from the carotid artery), resulting in gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischemia were also significantly mitigated by rebamipide, in an indomethacin-sensitive manner, while irsogladine potently prevented such lesions without affecting the PD response, in a L-NAME-sensitive manner.

CONCLUSION: These results suggest that (1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa, (2) both irsogladine and rebamipide protect the stomach against injury caused by NH2Cl, and (3) the mechanism underlying the protective action of irsogladine is partly mediated by endogenous nitric oxide, while that of rebamipide is in part mediated by endogenous prostaglandins.

Keywords: irsogladine, rebamipide, monochloramine, gastric mucosal lesions, rats, comparative study