Structural basis of the antagonism between inorganic mercury and selenium in mammals

被引:145
作者
Gailer, J
George, GN
Pickering, IJ
Madden, S
Prince, RC
Yu, EY
Denton, MB
Younis, HS
Aposhian, HV
机构
[1] Stanford Synchrotron Radiat Lab, SLAC, Stanford, CA 94309 USA
[2] Univ Arizona, Dept Cellular & Mol Biol, Tucson, AZ 85721 USA
[3] Univ Arizona, Dept Chem, Tucson, AZ 85721 USA
[4] ExxonMobil Res & Engn Co, Annandale, NJ 08801 USA
[5] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA
关键词
D O I
10.1021/tx000050h
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 Angstrom. 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.
引用
收藏
页码:1135 / 1142
页数:8
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