Rebamipide, an antiulcer drug, prevents DSS-induced colitis formation in rats.
This study was conducted to investigate the efficacy of rebamipide against experimental colitis induced by dextran sulfate sodium (DSS) in a rat model of inflammatory bowel disease. Experimental colitis was induced in male Wistar rats by oral administration of 3% DSS solution for one week. The rats were provided with standard diet containing 0.105% rebamipide (160 mg/kg/day) for 1 week. In rats treated with rebamipide, clinical (body weight loss, bloody diarrhea, reduced physical activity, severe anemia, shortened colonic length, and perianal injury) and histopathological (pathological lesion score) findings of DSS colitis were significantly less than in rats with DSS colitis not treated with rebamipide. Rebamipide thus inhibited the induction of colitis. Rebamipide significantly reduced concentrations of both interleukin-1alpha and GRO/CINC-1 (IL-8-like substance) and cell infiltrates in colonic wall, in parallel with decreased activity of myeloperoxidase. It also reduced expression of IL-1 mRNA but did not influence expression of GRO/CINC-1 mRNA. The attenuation of colonic indices of colitis by rebamipide in this rat model suggests that this drug might have beneficial effects in the treatment of human ulcerative colitis. These effects of rebamipide are attributable to its inhibition of inflammatory cytokine-mediated granulocyte (neutrophil) infiltration into the colon.
Kishimoto
S
S
Department of Geriatric Medicine, Institute of Health Sciences, Hiroshima University School of Medicine, Japan.
Haruma
K
K
Tari
A
A
Sakurai
K
K
Nakano
M
M
Nakagawa
Y
Y
D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000737:chemistry; D016264:Dextran Sulfate / Q000008:administration & dosage; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D009195:Peroxidase / Q000032:analysis; D015363:Quinolones / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000897:Anti-Ulcer Agents; D007375:Interleukin-1; D016209:Interleukin-8; D015363:Quinolones; D016264:Dextran Sulfate; D009195:Peroxidase; C052785:rebamipide; D000409:Alanine