Effect of icatibant, a bradykinin B2 receptor antagonist, on the development of experimental ulcerative colitis in mice.
Dextran sulfate sodium-induced colitis in mice has been recognized as a model for human ulcerative colitis. Using this model, we carried out a study on the preventive effect of Icatibant, a bradykinin B2 receptor antagonist previously called HOE 140, on the development of colitis. Subcutaneous administration of Icatibant (0.3 or 1.5 mg/kg) significantly suppressed shortening of the large intestine and worsening of the general health. Oral administration of Icatibant (50 mg/kg) significantly suppressed shortening of the large intestine, the onset of diarrhea, and worsening of the general health. In addition, the oral treatment significantly inhibited the development of colitis that was observed histopathologically. These results indicate a role of BK in the development of dextran sulfate sodium-induced colitis in mice, and suggest that BK could be important in human ulcerative colitis.
Arai
Y
Y
Project Management & Planning Department, Drug Innovation & Approval, Hoechst Marion Roussel Ltd., Tokyo, Japan.
Takanashi
H
H
Kitagawa
H
H
Wirth
K J
KJ
Okayasu
I
I
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000517:prevention & control*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D007279:Injections, Subcutaneous; D007420:Intestine, Large / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA
D000319:Adrenergic beta-Antagonists; D065168:Bradykinin Receptor Antagonists; C065679:icatibant; D016264:Dextran Sulfate; D001920:Bradykinin