Among the most startling observations in mammalian toxicology is that a lethal dose of selenium
can be overcome by an otherwise lethal dose of arsenic. We report the molecular basis of this antagonism.
Using X-ray absorption spectroscopy we have identified a new arsenic−selenium compound in the bile of
rabbits injected with aqueous selenite and arsenite solutions. This compound contains equimolar arsenic and
selenium and exhibits X-ray absorption spectra which are essentially identical with those of a synthetic species
in solution which we have identified spectroscopically as the seleno-bis(S-glutathionyl) arsinium ion. The in
vivo detection of this compound links the mammalian metabolism of arsenite, selenite, and sulfur. It provides
a molecular basis for the antagonistic interaction between these metalloid compounds, and a potential explanation
of the association of cancer with prolonged intake of inorganic arsenic in humans.
Mercuric chloride toxicity in mammals can be overcome by co-administration of sodium selenite. We report a study of the mutual detoxification product in rabbit plasma, and of a Hg-Se-S-containing species synthesized by addition of equimolar mercuric chloride and sodium selenite to aqueous, buffered glutathione. Chromatographic purification of this Hg-Se-S species and subsequent structural analysis by Se and Hg extended X-ray absorption fine structure (EXAFS) spectroscopy revealed the presence of four-coordinate Se and Hg entities separated by 2.61 A. Hg and Se near-edge X-ray absorption spectroscopy of erythrocytes, plasma, and bile of rabbits that had been injected with solutions of sodium selenite and mercuric chloride showed that Hg and Se in plasma samples exhibited X-ray absorption spectra that were essentially identical to those of the synthetic Hg-Se-S species. Thus, the molecular detoxification product of sodium selenite and mercuric chloride in rabbits exhibits similarities to the synthetic Hg-Se-S species. The underlying molecular mechanism for the formation of the Hg-Se-S species is discussed.
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