Document Detail


Suppressive effects of a new anti-inflammatory agent, IS-741, on dextran sulfate sodium-induced experimental colitis in rats.
MedLine Citation:
PMID:  11891534     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A novel anti-inflammatory drug, IS-741, blocked the adhesion of inflammatory cells to microvascular endothelial cells in vivo and in vitro. We examined the efficacy of IS-741 in a dextran sulfate sodium (DSS)-induced colitis model. DSS colitis was induced by the oral administration of 3% DSS for 10 days in rats. The rats were then divided in two groups: a 1% DSS plus IS-741 group and a 1% DSS plus water group. IS-741 was dissolved in water and administered orally (10 mg/kg) once per day for 14 days. The rats treated with DSS plus IS-741 remained healthy, and their body weight increased. The wet weight of the colon was significantly lower and the total colon length was significantly longer in the IS-741-treated group. Histological examinations revealed a marked infiltration of inflammatory cells into both the mucosa and submucosa in the DSS plus water group, but these changes were attenuated in the IS-741-treated group. The mucosal damage score was significantly reduced by treatment with IS-741. IS-741 also significantly reduced the mucosal myeloperoxidase activity. FACS analysis revealed that IS-741 significantly reduced Mac-1 expression on blood neutrophils. In conclusion, IS-741 suppressed DSS-induced experimental colitis in rats. Some of the action of IS-741 may be associated with its inhibitory effects on the Mac-1 expression of neutrophils in association with the blockade of their adhesion to endothelial cells. The findings in this study suggest that IS-741 may be a useful new therapeutic agent for inflammatory bowel disease.
Authors:
Jin Makino; Akira Andoh; Kazunori Hata; Shuichi Yotsuya; Hiroshi Shikama; Yoshio Araki; Yoshihide Fujiyama; Tadao Bamba
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  9     ISSN:  1107-3756     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-03-13     Completed Date:  2002-07-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  391-6     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Colitis, Ulcerative / chemically induced,  drug therapy*
Dextran Sulfate / toxicity
Endothelium, Vascular / metabolism
Macrophage-1 Antigen / biosynthesis
Male
Neutrophils / metabolism
Pyridines / pharmacology*
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/IS 741; 0/Macrophage-1 Antigen; 0/Pyridines; 9042-14-2/Dextran Sulfate

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