Effects of the neutrophil elastase inhibitor (ONO-6818) on acetic acid induced colitis in Syrian hamsters.

Neutrophil elastase (NE) released from neutrophils during inflammation is related to tissue disturbance and organ failure. We investigated the effects of an orally active NE inhibitor, ONO-6818, on acetic acid induced colitis in Syrian hamsters. The ulcer area, hemoglobin level in the colonic lumen, NE activity, and tissue myeloperoxidase (MPO) activity in the colitis control animals were significantly increased compared to the normal control ones. Either oral or subcutaneous treatment with ONO-6818 had significant inhibitory effects on the ulcer area, hemoglobin level and NE activity in the colonic lumen, but ONO-6818 did not have a significant inhibitory effect on tissue MPO activity. We conclude that NE is closely related to the development of inflammation in acetic acid-induced colitis in Syrian hamsters and that the condition is improved by the inhibition of NE.

[1]  T. Fujita,et al.  Colonic ulceration and increase of neutrophil elastase activity in the acetic acid-induced colitis model in Syrian hamsters. , 2004, The Journal of veterinary medical science.

[2]  J. Madara,et al.  Intestinal epithelial pathobiology: past, present and future. , 2002, Best practice & research. Clinical gastroenterology.

[3]  H. Ohbayashi.  Neutrophil elastase inhibitors as treatment for COPD , 2002, Expert opinion on investigational drugs.

[4]  L. W. Spruce,et al.  Design and synthesis of new orally active nonpeptidic inhibitors of human neutrophil elastase. , 2000, Journal of medicinal chemistry.

[5]  S. Nakao,et al.  Delayed neutrophil elastase inhibition prevents subsequent progression of acute lung injury induced by endotoxin inhalation in hamsters. , 2000, American journal of respiratory and critical care medicine.

[6]  J. D. de Paula,et al.  Colonic proteinases: increased activity in patients with ulcerative colitis. , 1998, Medicina.

[7]  I. Hirata,et al.  Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins. , 1996, The American journal of gastroenterology.

[8]  I. Hirata,et al.  The forms and the levels of fecal PMN-elastase in patients with colorectal diseases. , 1995, The American journal of gastroenterology.

[9]  K. Yoshimura,et al.  Roles of neutrophil elastase and superoxide anion in leukotriene B4-induced lung injury in rabbit. , 1994, Journal of applied physiology.

[10]  F. Dallegri,et al.  The drug 5-aminosalicylic acid rescues alpha 1-proteinase inhibitor from the neutrophil oxidative inactivation. A possible contribution to its therapeutic action in ulcerative colitis. , 1992, Digestion.

[11]  D. M. Cooke.  Inflammatory bowel disease: primary health care management of ulcerative colitis and Crohn's disease. , 1991, The Nurse practitioner.

[12]  M. Meyer,et al.  Elastase and papain inhibition by serum of mammals. , 1989, Scandinavian journal of clinical and laboratory investigation.

[13]  D. Jewell.  Corticosteroids for the management of ulcerative colitis and Crohn's disease. , 1989, Gastroenterology clinics of North America.

[14]  S. Weiss.  Tissue destruction by neutrophils. , 1989, The New England journal of medicine.

[15]  A. Janoff.  Elastase in tissue injury. , 1985, Annual review of medicine.

[16]  K. Havemann,et al.  Physiology and pathophysiology of neutral proteinases of human granulocytes. , 1984, Advances in experimental medicine and biology.

[17]  K. Yamamoto,et al.  Comparative studies on the serum levels of alpha-1-antitrypsin and alpha-macroglobulin in several mammals. , 1983, The Tohoku journal of experimental medicine.

[18]  J. Travis,et al.  Enzymatic inactivation of human alpha-1-proteinase inhibitor by neutrophil myeloperoxidase. , 1979, Biochemical and biophysical research communications.

[19]  P. Fardella.  PLASMA HEMOGLOBIN. , 1964, Canadian journal of medical technology.

[20]  Truelove Sc,et al.  Treatment of ulcerative colitis with local hydrocortisone hemisuccinate sodium; a report on a controlled therapeutic trial. , 1958 .

[21]  S. Truelove.  Treatment of Ulcerative Colitis with Local Hydrocortisone , 1958, Proceedings of the Royal Society of Medicine.

[22]  S. Truelove,et al.  Treatment of Ulcerative Colitis with Local Hydrocortisone Hemisuccinate Sodium , 1957, British medical journal.