Protective effect of intra-rectal administration of rebamipide on dextran sulfate sodium-induced rat colitis.
OBJECTIVE
Rebamipide, an anti-ulcer drug, has various actions including radical scavenging and mucus-stimulating as well as anti-inflammatory effects, and exhibits both mucosal protective and healing promoting actions in the stomach. In the present study, we examined the effect of rebamipide on an animal model of colitis induced by dextran sulfate sodium (DSS).


METHODS
Experimental colitis was induced in rats by daily treatment with 3% DSS in drinking water for 7 days. Rebamipide (3-30 mg/kg), 5-aminosalicylic acid (5-ASA: 150 mg/kg) or metronidazole (10 and 30 mg/kg) was administered intra-rectally once daily for 6 days. The ulceration area, colon length, and mucosal myeloperoxidase (MPO) activity as well as thiobarbituric acid-reactive substance (TBARS) were measured on the 7th day after the onset of DSS treatment. The effects of rebamipide on the secretion of mucus in the colon was also examined.


RESULTS
DSS treatment caused severe lesions in the colon, accompanied by an increase in MPO activity and TBARS as well as a decrease in body weight gain and colon length. Repeated administration of rebamipide dose-dependently suppressed the colon lesions and improved the pathological changes induced by DSS treatment. Rebamipide significantly increased the mucus contents in the colon. Both 5-ASA and metronidazole also reduced the severity of DSS-induced lesions.


CONCLUSIONS
These results suggest that intra-rectal administration of rebamipide is effective against DSS-induced colitis. The protective effect of rebamipide may be attributable to both the radical scavenging action and the increase in the production of mucus in the colon, the latter presumably suppressing the process of intestinal bacterial infiltration.
Okayama
Mitsuaki
M
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Kyoto, Japan.
Tsubouchi
Ryoichi
R
Nishio
Hikaru
H
Kato
Shinichi
S
Takeuchi
Koji
K
D000285:Administration, Rectal; D000409:Alanine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control* / Q000662:veterinary; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D008297:Male; D015363:Quinolones / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000897:Anti-Ulcer Agents; D000925:Anticoagulants; D015363:Quinolones; D016264:Dextran Sulfate; C052785:rebamipide; D000409:Alanine