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Metallothionein overexpression does not protect against inflammatory bowel disease in a murine colitis model

Helieh S. Oz, Theresa Chen, Willem J.S. de Villiers, Craig J. McClain

Med Sci Monit 2005; 11(3): BR69-73

ID: 15372

Available online: 2004-08-09

Published: 2004-08-09

Background: We evaluated whether modulation of metallothionein (MT, and subsequent oxidative stress) would infl uence the development and progression of colitis.
Material/Methods: MT-transgenic (MT-TG), MT-knockout (MT-KO), and wild-type (WT) mice were treated with Dextran Sodium Sulfate (DSS) to induce colitis compared to controls (no DSS).
Results: The DSS treated MT-TG and MT-KO mice responded in a manner similar to that of DSS treated WT mice, with all groups developing severe colitis. The colonic MT content in DSS treated animals increased drastically when compared to controls. The colonic and blood levels of the antioxidant, glutathione (GSH), were signifi cantly reduced in DSS treated MT-TG and MT-KO mice. However,
there was no signifi cant difference in the cysteine levels in these mice. The subcellular level of MT was highest in intestinal crypts loci of MT-TG mice and was not observed in MT-KO mice as well as in
the inflammatory lesions.
Conclusions: We conclude that MT does not appear to infl uence the development or progression of intestinal pathology in the DSS animal model of IBD.

Keywords: Colitis - chemically induced, Colitis - metabolism, Colitis - pathology, Inflammatory Bowel Diseases - metabolism, Animals, Colitis - pathology, Colon - pathology, Dextran Sulfate, Disease Models, Animal, Gene Expression, Inflammatory Bowel Diseases - pathology, Metallothionein - metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic