Experimental ulcerative colitis impairs antioxidant defense system in rat intestine

Increasing attention has been given recently to the role of free radicals in the pathogenesis of ulcerative colitis, since the inflamed intestine is exposed to oxidative stress generated by infiltrating macrophages and neutrophils within the lamina propia. The overall goal of this study was to evaluate whether experimental ulcerative colitis induces significant changes in the antioxidant defense system in an experimental model induced by the intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid. Twenty rats were treated with 80 mg/kg body weight of trinitrobenzenesulfonic acid and 20 with the same volume of 0.9% NaCl. Rats were killed at one and two weeks after treatment to evaluate colon damage by light and electron transmission microscopy. The degree of tissue injury and inflammation was determined by measuring alkaline phosphatase, gamma-glutamyltranspeptidase, and myeloperoxidase activities and prostaglandin E2 and leukotriene B4. Glutathione levels and the activity of the enzymes of the antioxidant defense system were determined. Enzymatic markers of colon injury showed higher activities in rats with ulcerative colitis. Concentrations of prostaglandin E2 and leukotriene B4 were higher in the groups treated for one week with trinitrobenzenesulfonic acid and markers decreased after two weeks of treatment. All antioxidant enzyme activities were higher at one and two weeks after treatment; however, a significant decrease in total glutathione content was also observed. In conclusion, ulcerative colitis induced by trinitrobenzenesulfonic acid damages the intestinal mucosa and is accompanied by a shift in the antioxidant enzyme activities, and low levels of glutathione. This deficiency in glutathione could be a target for new therapies to treat ulcerative colitis.