1 Single, very low dose of gold (500 μg/kg body weight) was given intramuscularly to male Sprague-Dawley rats (mean body weight: 200 g) as aurothiokeratinate (Auro-Detoxin dissolved in 0.9% NaCl.
2 Blood, liver and kidney were samples at autopsy 0.5,1, 2, 3, 6 and 12 h after the gold injection (six animals per time). 12 rats were treated with 0.9% saline only as controls. The zinc (Zn), copper (Cu), gold and metallothionein (MT) concentrations were determined in homogenates and cytosols of liver and kidney using atomic absorption spectrometry and gel chromatogra phy, respectively.
3 The main changes in metal and MT concentrations occurred in the kidney, where an increase of gold was found 0.5 h after the injection, followed by an increase in Cu and MT concentrations after 6 h. Zn homeostasis did not change.
4 The results suggest that gold by itself induces an increase of MT-like peptides in the kidney cytosol, which was accompanied by an increase in the concentration of Cu mainly bound to these MT-like peptides.
Research Sub-Committee of the Empire Rheumatism Council.Gold therapy in rheumatoid arthritis. Final report of a multicentre controlled trial. Annals of the Rheumatic Diseases1961; 20: 315-334.
2.
Research Sub-Committee of the Empire Rheumatism Council.Relation of toxic reactions in gold therapy to improvement in rheumatoid arthritis. Annals of the Rhuematic Diseases1961; 20: 335-340.
3.
Singler JW, Bluhm GB, Duncan H.Gold salts in the treatment of rheumatoid arthritis: a double-blind studie . Annals of internal Medicine1974; 80: 21-26.
4.
Mason RWTime course of gold-induced accumulation of copper and zinc and the effects of dimercaptosuccinate and cadmium on gold metabolism in rat kidney. Chemico-BiologicalInteractions1983; 43: 199-208.
5.
Sharma RPMetabolism of intracellular zinc and coppper following single and repeated injections of gold sodium thiomalate. Agents Actions1983; 13: 380-388.
6.
Mogilnicka EM , Webb M.Time-dependent uptake and metallothionein binding of gold, copper and zinc in the rat kidney. Biochemical Pharmacology1983; 32: 1341-1346.
7.
McVety KJ, Shaikh ZASubchronic treatment of rats with aurothioglucose; effects on plasma, hepatic, renal and urinary zinc, copper and metallothionein. Toxicology1987; 46: 295-306.
8.
Piscator M.Of cadmium in normal human kidneys together with a report of the isolation of metallothionein from livers of cadmium-exposed rabbits. Nordisk Hygienisk Tidsskrift1964; 45: 76-82.
9.
Kägi JHR, Nordberg M (eds.). Metallothionein: Proceedings of first international meeting of metallothionein and other low molecular weight metal-binding proteins . Basel: Birkhäuser Verlag, 1979.
10.
Sharma RP, McQuenn EGThe effect of zinc and copper pretreatment in the binding of gold (I) to hepatic and renal metallothioneins. Biochemical Pharmacology1982; 31: 2153-2159.
11.
Cousins RJAbsorption, transport and hepatic metabolism of copper and zinc. Special reference to metallothionein and ceruloplasmin. Physiological Reveiws1985; 65: 238-309.
12.
Thornally PJ , Vasak M.Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. Biochimica et Biophysica Acta1985; 827: 36-44.
13.
Webb M., Cain C.Functions of metallothionein. Biochemical Pharmacology1982; 31: 137-142.
14.
Bremner I.Involvement of Metallothionein in the hepatic metabolism of copper. Journal of Nutrition1987; 117: 19-29.
15.
Kägi Jhr.Overview of metallothionein. Methods in Enzymology1991; 205: 613-626.
16.
Koizumi T. et al. Protective effect of metallothionein on intracellular pH changes induced by cadmium. Toxicology1995; 95: 11-17.
17.
Pasquier C. et al. Superoxide dismutases in polymorphonuclear leukocytes from patients with ankylosing spondylitis and rheumatoid arthritis . Clinical and Experimental Rheumatology1985 ; 3: 123-126.
18.
Rae KJ et al. Early and late changes in sulphydryl group and copper protein concentrations and activities during drug treatment with aurothiomalate and auranofin. Annals of the Rheumatic Diseases1986; 45: 839-846.
19.
Rafter GWRheumatoid arthritis: a disturbance in copper homeostasis. Medical Hypotheses1987; 22: 245-249.
20.
Rayton JK, Harris EDInduction of lysyl oxidase with copper: Properties of an in vitro system. Journal of Biological Chemistry1979; 254: 621-626.
21.
Bird HAHeavy metals and arthritis. Annals of the Rheumatic Diseases1983; 42: 474-475.
22.
Milanino R. et al. Copper and zinc body levels in inflammation: an overview of the data obtained from animal and human studies. Agents Actions1993; 39: 195-209.
Kotz R., Kaiser G., Tschöpel F., Tölg G.AufschluB biologischer Matrices für die Bestimmung sehr niedriger Spurenelementgehalte bei begrenzter Einwaage mit Salpetersäure unter Druck in einem Teflongefäß. Zeitschrift für AnalytischeChemie1972 ; 260: 207-209.
25.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJProtein measurement with the Folin phenol reagent. Journal of Biological Chemistry1951; 193: 265-275.
Bodgen JD, Jortner BS, Kemp FW, Zadzielski E.Effect of aurothioglucose on liver and kidney concentrations of copper, iron manganese and zinc. Toxicology1981; 19: 21-29.
29.
Mogilnicka EM, Webb M.Comparative studies on the distribution of gold, copper and zinc in the livers and kidneys of rats and hamsters after treatment with sodium auro-thiomalate. Journal of Applied Toxicology1981; 1: 287-291.
30.
Mogilnicka EM, Webb M.The tissue distribution of gold, copper and zinc in animals treated with AuIII); Species differences in the binding of these metals in the kidney. Journal of Applied Toxicology1981; 1: 42-49.
31.
Szymanska JA , Zelazowski AJEffect of cadmium, mercury and bismuth on the copper content in rat tissues. Environmental Research1979; 19: 121-128.
32.
Mogilnicka EM, Webb M.The effects of cadmium and copper on the renal uptake and metallothionein binding of gold in the rat and hamster. Chemico-Biological Interactions1982; 40: 247-256.
