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The Role of Zinc and Metallothionein in the Dextran Sulfate Sodium-Induced Colitis Mouse Model


Zinc (Zn) and its binding protein metallothionien (MT) have been proposed to suppress the disease activity in ulcerative colitis. To determine the role of Zn and MT in the dextran sulfate sodium (DSS)-induced model of colitis in mice, a DSS dose-response study was conducted in male C57BL/6 wild-type (MT+/+) and MT-null (MT−/−) mice by supplementing 2%, 3%, and 4% DSS in the drinking water for 6 days. In the intervention study, colitis was induced with 2% DSS, Zn (24 mg/ml as ZnO) was gavaged (0.1 ml) daily, concurrent with DSS administration, and the disease activity index (DAI) was scored daily. Histology, MT levels, and myeloperoxidase (MPO) activity were determined. DAI was increased (P<0.05) by 16% and 21% with 3% and 4% concentrations of DSS, respectively, compared to 2%, evident after 5 days of DSS administration. MPO activity was increased in MT+/+ compared to MT−/− mice and those receiving DSS. Zn administration had a 50% (P<0.05) lower DAI compared to DSS alone. Zn partially prevented the distal colon of MT+/+ by 47% from DSS-induced damage compared to MT−/− mice. MT did not prevent DSS-induced colitis and Zn was partially effective in amelioration of DSS-induced colitis.

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The authors would also like to thank Ms. Kerry Lymn and Mr. Chad Mauger for technical assistance throughout the project and Mr. Mark Geier for assistance with histological analysis. This work was supported by the National Health and Medical Research Council Industry Fellowship to Dr. Tran.

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Correspondence to C. D. Tran.

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Tran, C.D., Ball, J.M., Sundar, S. et al. The Role of Zinc and Metallothionein in the Dextran Sulfate Sodium-Induced Colitis Mouse Model. Dig Dis Sci 52, 2113–2121 (2007).

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  • Inflammatory bowel disease
  • DSS-induced colitis
  • Zinc
  • Metallothionein (MT)
  • MT knockout