Non-peptidyl low molecular weight radical scavenger IAC attenuates DSS-induced colitis in rats

Abstract

To investigate the effects of the free radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate (IAC) in the dextran sodium sulphate (DSS) experimental model of ulcerative colitis. Colitis was induced in Sprague Dawley male rats by administration of 5% DSS in drinking water. IAC (30 mg/kg, lipophilic or hydrophilic form) was administered daily (orally or ip) for 6 d until sacrifice. Colonic damage was assessed by means of indirect (Disease Activity Index score) and direct measures (macroscopic and microscopic scores) and myeloperoxidase (MPO) activity. Neutrophil infiltration within the tissue and glutathione S-transferase activity were also investigated. DSS-induced colitis impaired body weight gain and markedly increased all inflammatory parameters. Six-day treatment with lipophilic IAC significantly reduced intestinal damage caused by inflammation, induced a down-regulation in MPO activity (0.72 +/- 0.12 and 0.45 +/- 0.12 with lipophilic IAC po and ip, respectively, vs 1.10 +/- 0.27 in untreated DSS colitis animals) and minimized DSS-induced neutrophil infiltration, while hydrophilic IAC administered orally did not ameliorate DSS-induced damage. These results support the hypothesis that reactive oxygen metabolites contribute to inflammation and that the radical scavenger IAC has therapeutic potential in inflammatory bowel disease.