Brief Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Sep 28, 2011; 17(36): 4099-4103
Published online Sep 28, 2011. doi: 10.3748/wjg.v17.i36.4099
Antioxidative potential of a combined therapy of anti TNFα and Zn acetate in experimental colitis
Michela Barollo, Valentina Medici, Renata D’Incà, Antara Banerjee, Giuseppe Ingravallo, Marco Scarpa, Surajit Patak, Cesare Ruffolo, Romilda Cardin, Giacomo Carlo Sturniolo
Michela Barollo, Renata D’Incà, Antara Banerjee, Surajit Patak, Cesare Ruffolo, Romilda Cardin, Giacomo Carlo Sturniolo, Department of Surgical and Gastroenterological Sciences, University of Padova, Padova 35128, Italy
Valentina Medici, Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of California, Davis, CA 95616, United States
Giuseppe Ingravallo, Department of Pathology, University of Bari, Bari 70121, Italy
Marco Scarpa, Department of Oncological Surgery, Veneto Oncological Institute, Padova 35128, Italy
Author contributions: Barollo M and Medici V designed the study and wrote the manuscript; Scarpa M and Ruffolo C performed the experiments and the statistical analysis; Banerjee A, Patak S revised the manuscript; D’Incà R and Sturniolo GC designed the study and revised the manuscript; Cardin R performed the biochemical analysis; Ingravallo G carried out the histological analysis.
Supported by MIUR 40% University of Padova
Correspondence to: Giacomo Carlo Sturniolo, MD, Professor of Gastroenterology, Department of Gastroenterology, Via Giustiniani 2, Padova 35128, Italy. gc.sturniolo@unipd.it
Telephone: +39-49-8218726   Fax: +39-49-8760820
Received: December 15, 2010
Revised: February 19, 2011
Accepted: February 26, 2011
Published online: September 28, 2011
Abstract

AIM: To evaluate whether combination therapy with anti-tumour 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.

Keywords: Anti tumor necrosis factor α, Experimental colitis, Inflammatory bowel disease, Oxidative damage, Zinc