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

AIM: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.METHODS: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.RESULTS: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.CONCLUSION: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.