The free radical scavengers edaravone and tempol suppress experimental dextran sulfate sodium-induced colitis in mice.
Recent studies have suggested that the enhanced release of reactive oxygen species (ROS) plays an important role in the pathogenesis of clinical inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease. In the present study, we investigated the effects of the free radical scavengers edaravone and tempol in the development of experimental dextran sulfate sodium (DSS)-induced colitis in mice. Male BALB/cA mice were fed 4% (w/w of diet) DSS in standard powder chow for 8 days. Edaravone, tempol, or vehicle saline were then injected subcutaneously twice per day. After the experimental period, the colonic length, histological damage score, and mucosal myeloperoxidase (MPO) and serum interleukin-6 (IL-6) levels were measured. Edaravone (15 mg/kg/day) and tempol (5-15 mg/kg/day) suppressed the colonic shortening and the damage score. In particular, tempol at 15 mg/kg/day significantly attenuated the colonic shortening and damage score. Edaravone and tempol suppressed the serum IL-6 levels, and significantly suppressed the increased colonic MPO levels. These results strongly support the involvement of ROS in the pathogenesis of DSS-induced colitis. A clinical effect for edaravone and tempol in IBD patients is strongly expected.
Araki
Yoshio
Y
Department of Internal Medicine, Biwako Youikuin Hospital, Otsu 520-2144, Japan. bileacidaraki@hotmail.com
Sugihara
Hiroyuki
H
Hattori
Takanori
T
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003092:Colitis / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D016264:Dextran Sulfate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000097:blood; D013113:Spin Labels
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D015850:Interleukin-6; D013113:Spin Labels; D016264:Dextran Sulfate; D009195:Peroxidase; D000077553:Edaravone; D000983:Antipyrine; C001803:tempol