The role of zinc (Zn) and metallothionein (MT) in dextran sulfate sodium (DSS)‐induced colitis in MT‐null (MT−/−) and wild‐type mice

Abstract

Introduction: Zinc (Zn) and its binding protein metallothionien (MT) have been proposed to suppress the disease activity of ulcerative colitis. The aim of the present is to determine the role of Zn and MT in the dextran sulfate sodium (DSS)-induced model of colitis in mice. Methods: 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 d. In the intervention study, colitis was induced by 2% DSS, Zn (24 mg/ml as ZnO) was gavaged (0.1 ml) daily, concurrent with DSS administration, and the disease activity index (DAI) scored daily. Histology, MT levels and myeloperoxidase (MPO) activity were determined. Results: DAI was increased (p<0.05) by 16% and 21% with 3% and 4% concentrations of DSS, respectively compared to 2%, evident after 5 d 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 damaged compared to MT−/− mice. Conclusions: MT did not prevent DSS-induced colitis and Zn was partially effective in amelioration of DSS-induced colitis.