The effects of silver ions on copper metabolism in rats

• Published in: Metallomics Vol. 6; no. 1; pp. 197 - 1987
• Main Authors: Ilyechova, E. Yu, Saveliev, A. N, Skvortsov, A. N, Babich, P. S, Zatulovskaia, Yu. A, Pliss, M. G, Korzhevskii, D. E, Tsymbalenko, N. V, Puchkova, L. V
• Format: Journal Article
• Language: English
• Published: England 01-10-2014
• Subjects: Animals; Ceruloplasmin - analysis; Ceruloplasmin - metabolism; Copper - blood; Copper - metabolism; Diet; Female; Gene Expression Regulation - drug effects; Liver - metabolism; Male; Rats; Silver - administration & dosage; Silver - blood; Silver - pharmacokinetics; Silver - pharmacology
• ISSN: 1756-5901; 1756-591X
• DOI: 10.1039/c4mt00107a

The influence of short and prolonged diet containing silver ions (Ag-diet) on copper metabolism was studied. Two groups of animals were used: one group of adult rats received a Ag-diet for one month (Ag-A1) and another group received a Ag-diet for 6 months from birth (Ag-N6). In Ag-A1 rats, the Ag-diet caused a dramatic decrease of copper status indexes that was manifested as ceruloplasmin-associated copper deficiency. In Ag-N6 rats, copper status indexes decreased only 2-fold as compared to control rats. In rats of both groups, silver entered the bloodstream and accumulated in the liver. Silver was incorporated into ceruloplasmin (Cp), but not SOD1. In the liver, a prolonged Ag-diet caused a decrease of the expression level of genes, associated with copper metabolism. Comparative spectrophotometric analysis of partially purified Cp fractions has shown that Cp from Ag-N6 rats was closer to holo-Cp by specific enzymatic activities and tertiary structure than Cp from Ag-A1 rats. However, Cp of Ag-N6 differs from control holo-Cp and Cp of Ag-A1 in its affinity to DEAE-Sepharose and in its binding properties to lectins. In the bloodstream of Ag-N6, two Cp forms are present as shown in pulse-experiments on rats with the liver isolated from circulation. One of the Cp isoforms is of hepatic origin, and the other is of extrahepatic origin; the latter is characterized by a faster rate of secretion than hepatic Cp. These data allowed us to suggest that the disturbance of holo-Cp formation in the liver was compensated by induction of extrahepatic Cp synthesis. The possible biological importance of these effects is discussed.
The serum ceruloplasmin-associated copper deficiency induced by a silver-containing diet in rats can be compensated by extrahepatic ceruloplasmin synthesis if rats receive silver from birth.