Relationship between ceruloplasmin and Cu status involving metallothionein induced by several heavy metals in the mouse.

ICR male mice aged 5 weeks were injected subcutaneously with CdCl2, Pb(CH3COO)2, AgNO3, CuCl2, a combination of Cd and Ag compounds, or a combination of Cu and Ag compounds. These injections were carried out 3 times. Twenty-four hours after the last injection, they were sacrificed. Cd injection significantly stimulated serum ceruloplasmin (Cp) activity and Cu concentration, accompanied by an increase in hepatic Cu. Pb injection also slightly increased the Cp level. In contrast, Ag injection markedly decreased both Cp activity and Cu concentration in the serum. Hepatic Cu increased slightly after Ag injection. Using a combination of Cd and Ag, only the Ag effect on the Cp activity appeared. The Cu injection stimulated Cu binding to metallothionein (MT) and bile excretion of Cu, but not Cp release. With a Cu and Ag combination, the effect of Ag on Cp was lost, with a concomitant disappearance of Ag from the Cp fraction in the serum. Our results suggest that in the mouse, Cd and Ag, Cu antagonistic metals, influence different sites of Cp metabolism. Excess hepatic Cu is partly eliminated by excretion of bile and is partly detoxified by MT induction.