Oral administration of mesalazine protects against mucosal injury and permeation in dextran sulfate sodium-induced colitis in rats.
OBJECTIVE. Mesalazine, from which 5-aminosalicylic acid is released, is a therapeutic drug for inflammatory bowel disease. There has been no study concerning the effect of orally administered mesalazine on dextran sodium sulfate (DSS)-induced colitis in the rat model of ulcerative colitis. MATERIAL AND METHODS. Colitis was evaluated by means of the length of the colon, white blood cell count (WBC), tissue myeloperoxidase (MPO) activity, and histological inflammation scores. Colonic mucosal permeation was evaluated using Evans blue. The localization of a tight junction protein, occludin, was evaluated immunohistochemically and examined using confocal laser scanning microscopy. RESULTS. Mesalazine significantly improved changes in the length of the colon, tissue MPO activity, WBC, and the histological inflammation score as compared with DSS-induced colitis. Furthermore, the drug completely inhibited the increased permeation in DSS-induced colitis in rats. The immunofluorescence signals of occludin were disrupted and irregularly distributed in DSS-induced colitis, while the signals appeared as a typical reticular pattern but with reduced intensity by the administration of mesalazine, without any reduction in the protein content. In addition, the oral administration of mesalazine significantly improved mucosal permeation, thereby protecting the intestinal mucosa against injury in DSS-induced colitis in rats. CONCLUSIONS. These findings suggest that the recovery of mucosal impairment due to treatment with mesalazine may be associated with the protection of the tight junction protein occludin in DSS-induced colitis.
Hayashi
Yoshihiro
Y
Department of Gastroenterology and Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
Aoyagi
Kunihiko
K
Morita
Isamu
I
Yamamoto
Chifumi
C
Sakisaka
Shotaro
S
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016264:Dextran Sulfate / Q000493:pharmacokinetics / Q000633:toxicity; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine; D016264:Dextran Sulfate