Effects of the non-peptidyl low molecular weight radical scavenger IAC in DNBS-induced colitis in rats.

ABSTRACT

Intestinal inflammation is accompanied by excessive production of reactive oxygen and nitrogen radical species because of the massive infiltration of polymorphonuclear and mononuclear leukocytes. Antioxidant compounds seem to protect against experimental colitis. Here we investigated the effects of the innovative non-peptidyl, low molecular weight radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate (IAC), which is highly reactive with most oxygen, nitrogen and carbon centred radicals and is easily distributed in cell membranes and intra-extra cellular compartments, in the DNBS model of colitis. Colitis was induced in male SD rats by intrarectal administration of DNBS (15 mg/rat). IAC (30 mg/kg b.w., hydrophilic or lipophilic form) was administered daily (orally or i.p.) starting from the day before the induction of colitis for 7 days (n=6-8 per group). Colonic damage was assessed by means of macroscopic and histological scores, myeloperoxidase activity (MPO) and TNF-alpha tissue levels. Colitis impaired body weight gain and markedly increased all inflammatory parameters. IAC significantly counteracted the reduction in body weight gain, decreased colonic damage and inflammation and TNF-alpha levels in DNBS-colitis. The antioxidant IAC significantly ameliorates experimental colitis in rats. This strengthens the notion that antioxidant compounds may have therapeutic potential in inflammatory bowel disease.