Antioxidative potential of a combined therapy of anti TNFα and Zn acetate in experimental colitis

AIM：To evaluate whether combination therapy with antitumour necrosis factor α （TNFα） 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 μg anti-TNFα treated group;Zn acetate treated group ＋ DSS ＋ subcutaneous 25 μg anti-TNFα;standard diet ＋ DSS ＋ subcutaneous 6.25 μg anti-TNFα treated group and Zn acetate treated group ＋ DSS ＋ subcutaneous 6.25 μg anti-TNFα.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 （8OH-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-TNFα 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-TNFα.Combining anti-TNFα with Zn acetate offers marginal benefit in colitis severity.