The importance of oxygen free radicals in the etiopathogenesis of diversion colitis in rats

Abstract

PURPOSE: Quantify the levels of oxidative DNA damage of epithelial colon cells comparing segments with and without fecal stream. METHODS: Sixty Wistar rats were subjected to deviation of fecal stream by proximal colostomy and a distal mucosal fistula. Animals were divided into three experimental groups that were sacrificed 6, 12 and 24 weeks after surgery. In each experimental group, five animals underwent laparotomy without intestinal deviation (sham subgroup). The diagnosis of colitis was made by histopathological analysis and the inflammatory activity index by graduated scale. The neutrophil infiltration was determined by myeloperoxidase tissue levels and the intensity of oxidative DNA damage by comet assay. The Mann-Withney and Student t test were used to compare the results among experimental subgroups and the Kruskal-Wallis test for variance analysis, adopting a significance level of 5% (p<0.05). RESULTS: Colon segments without fecal stream was shown higher histological inflammatory score of the colon wall after 12 and 24 weeks (p=0.001) that increased with the time of diversion (p=0.01). The activity of myeloperoxidase in segments without fecal stream decreased with the time (p=0.001). Oxidative DNA damage levels were significantly higher in the segments without fecal stream, (p=0.0001), independent of time of colon diversion, and increase with the time (p=0.0007). CONCLUSIONS: Colon segments without fecal stream showed high levels of oxidative DNA damage related to histological alterations observed in diversion colitis. The levels of oxidative DNA damage in segments devoid of the fecal stream increase with the time of intestinal exclusion.