The effect of zinc and copper pretreatment on the binding of gold (I) to hepatic and renal metallothioneins.
In the first part of this study, single s.c. injections of gold (I) sodium thiomalate were given to male Wistar rats at various dose levels and sacrificed either at 48 hr or 4 days later. The results indicate that though metallothioneins play a significant role in the sequestration of renal gold, the ability of gold itself to induce synthesis of the metalloprotein was limited in the kidneys and practically insignificant in the liver. Pre-injection with zinc however, (4 mg/kg body wt), significantly (P less than 0.01) enhanced the uptake of gold into the metallothioneins both, in the liver as well as the kidneys. The pretreatment increased the proportion of cytosolic gold incorporated into the thioneins from 29% to 48% in the kidneys and from 22% to 47% in the liver. Concurrent increases in the uptake of zinc and copper into the thioneins was also observed. Pre-injection with copper induced a similar effect in the kidneys only. There was no significant difference in the overall uptake of gold into the cytosol itself between the control animals (injected with gold only) and those pretreated with either zinc or copper. This indicated that the increased uptake of gold into the thioneins in the pretreated animals were due to enhanced synthesis of metallothioneins and subsequent increased binding of gold to thioneins rather than increased levels of intracellular gold itself. It is suggested that increased protection against the deposition and possible toxicity of gold in the cell organelles of the liver and kidney tissues may be provided by an increased binding of gold to metallothioneins through pretreatment with zinc, and to a lesser extent copper.
D000818:Animals; D003300:Copper / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D006046:Gold / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008667:Metalloproteins / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000494:pharmacology*
D008667:Metalloproteins; D006046:Gold; D003300:Copper; D008668:Metallothionein; D015032:Zinc