Effect of Silver Ions on Copper Metabolism during Mammalian Ontogenesis

Copper metabolism was studied in laboratory rats that received silver ions with food (Ag diet) from birth for 5, 20, 40, and 180 days. Parameters of the copper status in the blood serum were determined, and data on the distribution of silver ions in the body were obtained. A comparative histological analysis of brain, liver, kidney, and spleen sections of adult rats kept on the Ag diet for 30 or 180 days was performed. Copper and silver content, expression levels of the genes of copper transport proteins, and the activity of copper enzymes were determined in the cells of the liver, the central organ responsible for copper metabolism in mammals. In adult rats kept on the Ag diet for 30 days, copper status parameters dropped to near-zero values. In contrast, these parameters were decreased only twofold in rats that had been kept on the Ag diet for 6 months from birth. At the same time, the expression of genes involved in copper homeostatis was downregulated. The expression of genes that encode copper enzymes was unchanged. The activity of ceruloplasmin, the main copper-containing protein of the blood, was decreased, while the activity of SOD1, a cellular copper enzyme, was unchanged. The pathways by which silver can interfere with copper metabolism and the mechanisms that compensate these effects are discussed. The data obtained may help assess the potential consequences of growing environmental exposure to silver due to increasing use of silver nanoparticles in different areas of human activity.