Effect of argatroban on trinitrobenzene sulfonic acid-induced colitis.
BACKGROUND
Recent studies have suggested that heparin is effective for treatment of inflammatory bowel disease (IBD) and its various effects (in addition to the anticoagulant effect). We evaluated the effects of argatroban as an antithrombin drug on trinitrobenzene sulfonic acid (TNB)-induced colitis, an established model of IBD.


METHODS
Rats were randomly assigned to four groups in which mini-osmotic pumps containing saline (TNB-S), argatroban (TNB-A), or 100 U/kg heparin (TNB-H) were intraperitoneally implanted. Three days after the pumps were implanted, TNB was infused via the anus, and colitis was induced. After 5 days, prothrombin time (PT), activated partial prothrombin time (APTT), antithrombin III (AT-III), platelet, fibrinogen, colonic wet weight, macroscopic damage score, histological score, mucosal myeloperoxidase activity and mucosal leukotrien B4 (LTB4) levels were compared among the four groups.


RESULTS
The APTT was prolonged in the heparin treatment group but only slightly prolonged in the argatroban treatment group. The platelet count and the fibrinogen level were higher in the TNB-S group than in the healthy control group and the AT-III level was slightly lower in the TNB-S group than in the healthy control group and lower still in the TNB-H group.


CONCLUSIONS
The colonic wet weight was similar among the four groups while the macroscopic damage score, histological score, mucosal myeloperoxidase activity and the mucosal LTB4 level were significantly decreased in the TNB-A and TNB-H groups. Argatroban, as well as heparin may be effective for treatment of TNB-induced colitis.
Onomura
M
M
Department of Metabolism and Clinical Nutrition, Faculty of Medicine, Kyoto University, Japan. onomura@metab.kuhp.kyoto-u.ac.jp
Tsukada
H
H
Fukuda
K
K
Kodama
M
M
Nakamura
H
H
Hosokawa
M
M
Ohya
M
M
Seino
Y
Y
D000704:Analysis of Variance; D000818:Animals; D000991:Antithrombins / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D001780:Blood Coagulation Tests; D003092:Colitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D006493:Heparin / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D015918:Infusion Pumps, Implantable; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D009578:Nitrobenzenes; D009195:Peroxidase / Q000378:metabolism; D010875:Pipecolic Acids / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides; D013451:Sulfonic Acids
D000991:Antithrombins; D009578:Nitrobenzenes; D010875:Pipecolic Acids; D013449:Sulfonamides; D013451:Sulfonic Acids; D007975:Leukotriene B4; D006493:Heparin; D001120:Arginine; D009195:Peroxidase; C031942:argatroban