Metabolism of intracellular zinc and copper following single and repeated injections of gold sodium thiomalate.

Abstract

Repeated injections of gold sodium thiomalate were given to Wistar rats and the effect of gold on the binding of endogenous zinc and copper to the cytosolic proteins in the liver and kidneys was studied. The tissue levels of gold and the tissue uptake of zinc and copper as a function of gold dose was also studied. The result of the multiple-dose study show that in the liver the tissue gold levels rose rapidly following the first five gold injections (one injection/week) and then stabilized. In the kidneys the gold concentrations continued to increase with each additional dose. Uptake of zinc into the high molecular weight proteins (MW>60,000 daltons) and the superoxide dismutase fractions were significantly increased following the repeated gold injections in the liver and kidney cytosol. The uptake of copper into the high MW proteins were decreased in the liver as well as the kidneys. Copper levels in the superoxide dismutase and the low MW (<4000 daltons) fractions initially increased then decreased from the sixth gold dose onwards (possibly related to the overall decrease in tissue copper levels in the liver). The incorporation of copper into the hepatic metallothioneins appeared to be unaltered. In the kidney cytosol, the uptake of copper was significantly increased into the metallothionein fractions. The uptake into the other fractions decreased over the multiple-dose period. Gold sodium thiomalate increased the tissue concentration of zinc in the liver as well as the kidneys. The level of copper in the liver was decreased and that in the kidneys increased. Practically all the additional copper in the kidneys was incorporated in the thioneins. These observations indicate that gold sodium thiomalate has a major role in providing a stimulus for the liver, kidney and perhaps other cells to bring about a redistribution of body zinc and copper. The various cytosolic proteins, including the inducible metalloproteins, superoxide dismutase and metallothioneins, seem to help the cell carry out this task. In view of the importance of these essential metals in physiological processes of relevance to rheumatoid arthritis, it is suggested that gold salts may mediate, to some extent, their antiarthritic activity through an effect on the metabolism of zinc and copper.