Antioxidative potential of a combined therapy of anti TNF\u3b1 and Zn acetate in experimental colitis

AIM: To evaluate whether combination therapy with antitumour necrosis factor alpha (TNF alpha) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis. METHODS: Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d. The experimental mice were then randomised into the following subgroups: standard diet + DSS treated (induced colitis group); standard diet + DSS + subcutaneous 25 mu g anti-TNF alpha treated group; Zn acetate treated group + DSS + subcutaneous 25 mu g anti-TNF alpha; standard diet + DSS + subcutaneous 6.25 mu g anti-TNF alpha treated group and Zn acetate treated group + DSS + subcutaneous 6.25 mu g anti-TNF alpha. Each group of mice was matched with a similar group of sham control animals. Macroscopic and histological features were scored blindly. Homogenates of the colonic mucosa were assessed for myeloperoxidase activity as a biochemical marker of inflammation and DNA adducts (80H-dG) as a measure of oxidative damage. RESULTS: DSS produced submucosal erosions, ulcers, inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNF alpha alone or combined with zinc. The effect was more pronounced in the latter group (vs Zn diet, P < 0.02). Myeloperoxidase activity (vs controls, P < 0.02) and DNA adducts, greatly elevated in the DSS fed colitis group (vs controls, P < 0.05), were significantly reduced in the treated groups, with a more remarkable effect in the group receiving combined therapy (vs standard diet, P < 0.04). CONCLUSION: DSS induces colonic inflammation which is modulated by the administration of anti-TNF alpha. Combining anti-TNF alpha with Zn acetate offers marginal benefit in colitis severity. (C) 2011 Baishideng. All nghts reserved