Journal Article

Effects of Arsenic-, Platinum-, and Gold-Containing Drugs on the Disposition of Exogenous Selenium in Rats

Zoltán Gregus, Ágnes Gyurasics and Iván Csanaky

in Toxicological Sciences

Volume 57, issue 1, pages 22-31
Published in print September 2000 | ISSN: 1096-6080
Published online September 2000 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/57.1.22
Effects of Arsenic-, Platinum-, and Gold-Containing Drugs on the Disposition of Exogenous Selenium in Rats

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Having found that the electrophilic model compound sulfobromophthalein markedly altered the fate of exogenous selenium in the body by reacting in vivo with nucleophilic selenium metabolites, the effects of metal-containing drugs with expected selenium reactivity were tested on biliary, urinary, and pulmonary excretion. Tissue distribution of selenium in selenite-injected rats was also examined. Coadministration with [75Se]selenite (10 μmol/kg, iv) of the trypanosomicid arsenicals (100 μmol/kg, iv) trimelarsan (TMA) or melarsoprol (MAP), the antitumor cisplatin (25 μmol/kg, iv), or the antirheumatic gold sodium thiomalate (25 or 50 μmol/kg, iv) significantly altered the disposition of 75Se, whereas carboplatin (100 μmol/kg, iv) did not produce such an effect. The most dramatic alterations included the ∼ 20-fold increase in the biliary excretion rate of selenium in response to TMA and MAP, the almost complete cessation of the exhalation of selenium as dimethyl selenide after administration of the arsenic- and gold-containing drugs, and the manifold accumulation of selenium in the blood plasma following gold injection. Direct chemical reaction of the drugs with nucleophilic selenite metabolites in the body may underlie these alterations. The tight coordination in time and extent observed between the biliary excretion of arsenic and selenium in rats receiving either of the arsenicals and selenite supports this hypothesis. However, attempts to detect selenium-containing biliary metabolites of TMA and MAP have failed, possibly owing to their instability. In summary, the arsenic-, platinum- and gold-containing drugs significantly influence the fate of exogenous selenium, whereby they may adversely affect the availability of this essential element for synthesis of selenoenzymes. Furthermore, the capability of TMA and MAP to enhance the biliary and total excretion of selenium renders these drugs significant candidates for antidotes in selenium intoxication.

Keywords: selenium; arsenic; melarsoprol; cisplatin; gold; biliary excretion

Journal Article.  6669 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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