Suppressive effects of a new anti-inflammatory agent, IS-741, on dextran sulfate sodium-induced experimental colitis in rats.
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.
Makino
Jin
J
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Japan.
Andoh
Akira
A
Hata
Kazunori
K
Yotsuya
Shuichi
S
Shikama
Hiroshi
H
Araki
Yoshio
Y
Fujiyama
Yoshihide
Y
Bamba
Tadao
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy*; D016264:Dextran Sulfate / Q000633:toxicity; D004730:Endothelium, Vascular / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016177:Macrophage-1 Antigen; D011725:Pyridines; C097462:IS 741; D016264:Dextran Sulfate