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.
Hirota
Yasushi
Y
Fukui Safety Research Laboratories, Ono Pharmaceutical Co., Ltd., Fukui, Japan.
Suzuki
Mikie
M
Yamaguchi
Kojiro
K
Fujita
Tsuneo
T
Katsube
Nobuo
N
D019342:Acetic Acid / Q000633:toxicity*; D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy*; D006224:Cricetinae; D006454:Hemoglobins / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D010069:Oxadiazoles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D011744:Pyrimidinones / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015843:Serpins / Q000627:therapeutic use*
D006454:Hemoglobins; C419152:ONO 6818; D010069:Oxadiazoles; D011744:Pyrimidinones; D015843:Serpins; D009195:Peroxidase; D019272:Leukocyte Elastase; D019342:Acetic Acid