Dietary Copper Reduces the Hepatotoxicity of (−)-Epigallocatechin-3-Gallate in Mice

We developed Cu-deficient, -sufficient and -super nutrition mice models by feeding them with diet containing 1.68, 11.72 or 51.69 mg of Cu/kg for 28 days, respectively. Then, the mice were treated to (−)-epigallocatechin-3-gallate (EGCG, 750 mg/kg BW) by oral in order to assess the acute toxicity of the drug. Following EGCG treatment, the survival rates were 12.5%, 50% and 100% in the Cu-deficient, -sufficient and Cu-super nutrition groups of mice, respectively. Cu level and ceruloplasmin activity in serum were significantly increased with the increase of dietary Cu. However, the Cu supplementation did not produce any obvious impact on serum superoxide dismutase activity. Furthermore, ceruloplasmin, in vitro, significantly promotes EGCG oxidation accompanied with increasing oxidation products and decreasing levels of reactive oxygen species. These results, therefore, suggest that Cu can relieve EGCG hepatotoxicity, possibly by up-regulating ceruloplasmin activity, which can be used to promote EGCG applications.