The free radical scavenger edaravone suppresses experimental dextran sulfate sodium-induced colitis in rats.
Recent studies suggest that the enhanced release of reactive oxygen species (ROS) plays an important role in the pathogenesis of clinical inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. In the present study, we investigated the effects of the free radical scavenger edaravone, which is used clinically as an anti-stroke agent, in the development of experimental dextran sulfate sodium (DSS)-induced colitis in rats. The rats were fed 4% (w/w of diet) DSS in standard powder chow for 8 days. The edaravone and vehicle saline were injected subcutaneously twice a day. After the experimental period, the wet colonic weight, macroscopic mucosal damaged area, histological damage score, mucosal myeloperoxidase (MPO) activity, mucosal tissue lipid peroxidate and serum interleukin-6 (IL-6) levels were measured. In the DSS-induced colitis model, edaravone treatment (1-20 mg/kg day) significantly reduced the wet colonic weight, macroscopic damaged area, and the histological damage score. Edaravone treatment also reduced mucosal MPO activity, mucosal tissue lipid peroxidate level and serum IL-6 level. In particular, edaravone at a dose of 20 mg/kg day significantly reduced mucosal MPO activity and serum IL-6 level. These results strongly support the involvement of ROS in the pathogenesis of DSS-induced colitis. A clinical effect for edaravone against IBD patients is strongly expected.
Araki
Yoshio
Y
Ace Bio product Co, Chiyoda-ku, Tokyo, Japan. bileacidaraki@hotmail.com
Andoh
Akira
A
Fujiyama
Yoshihide
Y
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003092:Colitis / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000447:Aldehydes; D016166:Free Radical Scavengers; D015850:Interleukin-6; D008315:Malondialdehyde; D009195:Peroxidase; C027576:4-hydroxy-2-nonenal; D000077553:Edaravone; D000983:Antipyrine