Rebamipide enema is effective for treatment of experimental dextran sulfate sodium induced colitis in rats.
We investigated therapeutic efficacy of rebamipide using dextran sulfate sodium (DSS) induced colitis model in rats. Three percent DSS solution was given to rats for 9 days. After that, we evaluated the drug efficacy on colitis sustained with continuous drinking of 1% DSS. Twice-daily treatment with 0.3% or 1% rebamipide for 14 days significantly ameliorated the stool abnormality in the colitis model, preferentially suppressed hematochezia. The colonic mucosal lesion, determined by Alcian blue staining on day 24, was significantly reduced by rebamipide enema in a dose-dependent manner. Either rebamipide or 5-aminosalycilic acid (5-ASA) enema treated once daily significantly ameliorated colitis. The minimum effective dose of rebamipide was 0.3% in once-daily treatment, and that of 5-ASA was 10%. In a mechanistic study, the epithelial cell sheet formation of the T84 colon cancer cell was measured as an increase in generation of trans-epithelial electrical resistance in vitro. Rebamipide accelerated the increase, while 5-ASA conversely suppressed it. These results suggest that rebamipide enema is effective for treatment of experimental ulcerative colitis (UC).
Nakashima
Takako
T
Research Institute of Pharmacological and Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima 771-0192, Japan.
Maeda
Takashi
T
Nagamoto
Hisashi
H
Kumakura
Takeshi
T
Takai
Masaaki
M
Mori
Toyoki
T
D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000662:veterinary; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004733:Enema; D007202:Indicators and Reagents / Q000633:toxicity; D008297:Male; D019804:Mesalamine / Q000494:pharmacology; D015363:Quinolones / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D007202:Indicators and Reagents; D015363:Quinolones; D019804:Mesalamine; D016264:Dextran Sulfate; C052785:rebamipide; D000409:Alanine