Experimental ulcerative colitis impairs antioxidant defense system in rat intestine

Increasing attention has been given recently to the role of free radicals i n the pathogenesis of ulcerative colitis, since the inflamed intestine is e xposed to oxidative stress generated by infiltrating macrophages and neutro phils within the lamina propia. The overall goal of this study was to evalu ate whether experimental ulcerative colitis induces significant changes in the antioxidant defense system in an experimental model induced by the intr arectal administration of 2,4,6-trinitrobenzenesulfonic acid. Twenty rats w ere treated with 80 mg/kg body weight of trinitrobenzenesulfonic acid and 2 0 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 myelope roxidase activities and prostaglandin E-2 and leukotriene B-4. Glutathione levels and the activity of the enzymes of the antioxidant defense system we re determined. Enzymatic markers of colon injury showed higher activities i n rats with ulcerative colitis. Concentrations of prostaglandin E-2 and leu kotriene B-4 were higher in the groups treated for one week with trinitrobe nzenesulfonic acid and markers decreased after two weeks of treatment. All antioxidant enzyme activities were higher at one and two weeks after treatm ent; however, a significant decrease in total glutathione content was also observed. In conclusion, ulcerative colitis induced by trinitrobenzenesulfo nic acid damages the intestinal mucosa and is accompanied by a shift in the antioxidant enzyme activities, and low levels of glutathione. This deficie ncy in glutathione could be a target for new therapies to treat ulcerative colitis.