Role of metallothionein in cellular uptake and disposition of gold sodium thiomalate

Abstract

Rat liver and kidney tissue uptake of gold and its localization in the cytosol was studied following various doses of gold sodium thiomalate (GST). The timecourse of gold incorporation into intracellular gold-binding ligands following repeated injections of GST was also investigated (11 injections, one dose/week). Results show that between 30 and 60% of the hepatic and renal gold was localized in the cytosol over a wide range of GST doses. This was also true following repeated doses. In the kidney, the binding of gold to high molecular weight (HMW) proteins was saturated after the third GST dose, while incorporation into the metallothioneins (MT) continued to increase, accounting for as much as 50% of cytosolic gold. On the other hand the binding to hepatic MT was about 10x lower, and the proportion of cytosolic gold incorporated into the MT, decreased from 30% (after first 3 GST injections) to about 15% (following the last 3 injections). The results show that the stimulation of MT biosynthesis in different tissues as a response to the injected GST is not the same and varies within each organ with the dose and/or the duration of repeated exposure. In the liver, the ability of gold to induce MT synthesis was limited and the importance of MT in the cellular uptake and disposition of gold may largely be confined to the kidneys. It is suggested that besides playing a possible role in the detoxification of cellular gold, particularly in the kidney, MT may also contribute towards the retention and localization of gold in the tissues.

Species differences in the renal toxicity of the antiarthritic drug, gold sodium thiomalate

“…In the kidney, up to 50% of the cytosolic gold is incorporated into MT. Gold is also able to induce MT biosynthesis in the liver (3,23). As with Cd, the possibility exists that AuMT synthesized in the liver may be transported into the kidney.…”

Glial immunoreactivity for metallothionein in the rat brain

“…An enhanced MT content in these cells would be predicted to protect the hypothalamus from GTG, just as MT may have a role in protecting the area postrema from cis-platin. MT is known to diminish gold toxicity in other tissues (Laib et al, 1985;Sharma, 1984). Elevation of cellular metallothionein levels by administration of salicylate or small, non-toxic doses of gold can protect cells from toxic effects of metals given subsequently (Gunther et al, 1989;Sharma, 1984).…”