modulatory effects of some drugs with potential influence on oxidative cell damage on experimental ulcerative colitis

ABSTRACT

Ulcerative colitis is a chronic inflammatory bowel disease [IBD] where reactive oxygen species [ROS] are produced in excess. There are comparatively low tissue levels of endogenous antioxidants in the colonic mucosa. Oxidative stress occurred in IBD may therefore easily overwhelm the endogenous defenses that regulate ROS production. Our aim was to assess the ability of vitamins C, deferoxamine [Dfx] and amlodipine [Amlo] to inhibit colonic inflammation in dextran sulphate sodium [DSS]-induced colitis in rats. We used thirty mature male albino rats assigned to Group I normal control. Group II received DSS+0.5 ml 0.9% normal saline daily. Group III received DSS+vitamin C 100 mg/kg b.w./day. Group IV received DSS+amlodipine 3 mg/kg/day. Group V received DDS+Dfx 300 micro mol/kg/day. Acute colitis was induced by 3% DSS in drinking water for 7 days. Vitamin C, amlodipine, and deferoxamine were administered orally for 7 days before and a further 7 days during treatment with DSS. Rats without colitis received regular drinking water. On day 14 of drug treatment, colons were excised and opened longitudinally. Gross colonic mucosal injury were observed and scored. Colonic wet/dry weight ratios were calculated as an indirect index of the inflammatory reaction. Colonic myeloperoxidase [MPO] activity, glutathione [GSH] and Thiobarbituric acid-reactive substances were measured. The results of the present study showed that pretreatment of the rats with vitamin C, Amlo and Dfx reduced the gross mucosal injury developed after induction of colitis. These drugs prevented the increase in MPO activity produced in these cases of inflammation. Pretreatment of animals with vitamin C, Amlo or Dfx prevented the depletion of colonic GSH caused by DSS-induced colonic injury. All of the tested drugs were found also to decrease the enhanced lipid per oxidation observed in this model of DSS-induced colitis in rats. It can be concluded that pretreatment with vitamin C, amlodipine and deferoxamine can inhibit the inflammatory process in DSS-induced colitis in rats through their antioxidant properties