Organ distribution of silver and the effect of silver on copper status in rats

Tissue distribution of silver, alteration in tissue concentration of copper, zinc and iron, as well as changes in serum ceruloplasmin (CP) status were investigated in Fischer 344 rats after intraperitoneal (i.p.) administration of silver (9.3 mumol Ag/kg body wt.) as silver nitrate alone or combined with zinc (46.5 mumol Zn/kg) as zinc sulfate once a day for six successive days. Silver deposited in all the tissues examined, particularly in the pancreas, showing silver concentration in the serum, kidney, heart and lung to be significantly increased by simultaneous injection of zinc, while zinc concentration in the liver, pancreas and heart was significantly affected by silver. The most prominent effect of silver administration was observed in the copper status. As the result of altered copper metabolism by silver administration, copper concentration in the liver, pancreas and kidney was significantly changed, and serum copper concentration and CP oxidase activity were decreased to 60% and 25% of the control value, respectively. However, immunoblot analysis of serum CP in silver-treated groups showed only a slight decrease in protein levels, suggesting that most of the CP existed as an oxidase inactive apo-form. Simultaneously administered zinc hardly affected such changes. These results indicate that silver administration causes a disturbance of copper metabolism, and that zinc hardly plays a protective role against such changes.