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


CONCLUSIONS
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.
Department of Surgical and Gastroenterological Sciences, University of Padova, Padova 35128, Italy.
Michela
M
Barollo
Valentina
V
Medici
Renata
R
D'Incà
Antara
A
Banerjee
Giuseppe
G
Ingravallo
Marco
M
Scarpa
Surajit
S
Patak
Cesare
C
Ruffolo
Romilda
R
Cardin
Giacomo Carlo
GC
Sturniolo
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D004032:Diet; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D019345:Zinc Acetate / Q000008:administration & dosage / Q000627:therapeutic use*
D000906:Antibodies; D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D016264:Dextran Sulfate; D009195:Peroxidase; D019345:Zinc Acetate; D003849:Deoxyguanosine