[Effects of ulinastatin on experimental ulcerative colitis in rats].
We examined the effect of ulinastatin in comparison with prednisolone (PSL) and salazosulfapyridine (SASP), well-known drugs for ulcerative colitis (UC), on two experimental UC models induced by dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNB) in rats. Ulinastatin at the doses of 3000 approximately 10,000 units/kg/day (i.v.) significantly ameliorated the formation of erosion and infiltration of inflammatory cells in colonic mucosa in DSS-induced rat UC models. Moreover, ulinastatin at the dose of 10,000 units/kg/day (i.v.) significantly suppressed inflammation with ulcer in the colonic mucosa in TNB-induced rat UC models. PSL at the dose of 1 mg/kg/day (p.o.) also was as effective as ulinastatin on the above two UC models, while SASP at the dose of 100 mg/kg/day (p.o.) was less effective than ulinastatin and PSL. In addition, ulinastatin inhibited the activities of elastase and cathepsin G from human leukocytes, and it suppressed TNF alpha, IL-8 and superoxide production by rat macrophages and rabbit leukocytes in vitro. These results suggest that the suppression of inflammatory mediators produced by leukocytes is involved in the mechanism of the anti-UC action of ulinastatin.
Nagao
Y
Y
Biosciences Research Laboratory, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan.
Miyata
H
H
Mizuguchi
K
K
Ban
M
M
Kato
K
K
D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D007962:Leukocytes / Q000201:enzymology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012697:Serine Endopeptidases; D012460:Sulfasalazine / Q000627:therapeutic use; D014361:Trypsin Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D006023:Glycoproteins; D016209:Interleukin-8; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; D011239:Prednisolone; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; C534097:Ctsg protein, rat; D019272:Leukocyte Elastase; C028665:urinastatin