Effect of orally administered D‐penicillamine on gold deposited in the rat kidney

Abstract

Although orally administered D-penicillamine, a chelating agent, is known to enhance urinary excretion of gold in man, studies in experimental animals raised the possibility that renal deposition of gold might increase in the presence of the circulating gold-penicillamine complex. To investigate this possibility, rats previously treated with a gold salt were given a diet containing the chelating agent for a 28-day period. The renal content of gold was assayed at the end of the study period. The results showed that administration of D-penicillamine significantly enhanced the removal of gold from the kidneys.Ben que oralmente administrate Dpenicillamina (un agente de chelation) promove cognoscitemente le excretion urinari de auro in le homine, studios in animales experimental suggereva le possibilitate que le deposition renal de auro es augmentate in Ie presentia del circulante complexo de auro e penicillamina. Pro investigar iste possibilitate, rattos previemente tractate con un sal de auro esseva tractate con un dieta continente le agente de chelation durante un periodo de 28 dies. Le contento renal de auro esseva detreminate a1 fin del periodo. Le resultatos monstrava que le administration de D-penicillamina promoveva significativemente le elimination de auro ab le renes.ENCILLAMINE, a potent chelating agent, has been' shown to form a P stable complex with gold in vitro. When this complex was injected into rats, however, some gold was deposited in the kidneys, in'dicating that chelation did not completely protect the kidneys against deposition of go1d.l Studies in the rat have established that the kidney has a greater affinity for idjected soluble gold salts than any other organs or tissues.2 In human subjects, orally administered D-penicillamine enhances excretion of gold in the urine, presumably by mobilizing gold from many tissues.l It is theoretically possible, however, that as the circulating chelate passes through the kidney, significant amounts of either the gold-penicillamine complex or gold dissociated from the complex woiild be deposited in the renal tissue. If this were the case, the deposition of gold in the kidney, as well as uririary excretion of gold, would be increased. To investigate this possibility, a preliminary study was undertaken in rats. Dpenicillamine was added to the diet of rats previously injected with gold sodium thiomalate. The results of gold assays and histologic examidation of renal tissue from the treated animals are presented in this report.

Inhibition of adenosine triphosphatases by gold

“…We found 50% inhibitory concentration of gold for microsomal Na' + K' ATPase to be approximately lo-' to 10-6M. This is similar to the potency of ouabain, a classical specific inhibitor of Na' trapolated to the situation in vivo because of the following: 1) reduction of Au3+ to Au' can occur and the two oxidation states of gold behave differently toward the enzyme; 2) reduced metallic gold particles may be deposited in the kidney (27) with a loss of activity as an enzyme inhibitor; 3) gold ions bind to plasma (2) and tissue proteins, reducing the amount of inhibitor available to the enzyme; 4) gold stimulates the synthesis of metallothionein-like protein in the kidney which functions to reduce toxicity by binding metals (28); and 5 ) changes in acid-base balance may affect enzyme inhibition. However, it is reasonable to suggest that at some critical concentration of gold in tissues, the enzyme will become inhibited.…”