Therapeutic effects of ecabet sodium, an antiulcer drug, on dextran sodium sulfate-induced ulcerative colitis in rats.
Ecabet, an antiulcer drug, is reported to be effective in patients with ulcerative colitis. We investigated the effect of ecabet enema on ulcerative colitis in rats and some mechanisms underlying this effect. In vivo ecabet enema showed a therapeutic effect in the rat ulcerative colitis model induced by dextran sodium sulfate in the drinking water. The amount of ecabet bound to damaged mucosa was higher than that bound to normal mucosa 30 min after intrarectal administration. In vitro ecabet accelerated the restitution of epithelial cells, which was not affected by a TGF-beta antibody. Ecabet inhibited the leukotriene B4 production and 5-lipoxygenase activity in human neutrophils. In conclusion, ecabet enema showed a therapeutic effect in rats with ulcerative colitis. This effect may be attributable to the high binding affinity for damaged mucosa, the acceleration of restitution, and the inhibition of leukotriene B4 production.
Noto
Tsunehisa
T
Discovery & Pharmacology Research Laboratories, Toda, Saitama, Japan. t-noto@tanabe.co.jp
Yamada
Hiroshi
H
Inui
Takashi
T
Okuyama
Kayoko
K
Watanable
Ayako
A
Kimura
Isami
I
Nagasaki
Masaaki
M
D045784:Abietanes / Q000008:administration & dosage*; D000285:Administration, Rectal; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D018929:Cell Culture Techniques; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004733:Enema; D020895:Enterocytes / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D045784:Abietanes; D000897:Anti-Ulcer Agents; C061681:ecabet; D016264:Dextran Sulfate