Structural basis of the antagonism between inorganic mercury and selenium in mammals.
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.
Gailer
J
J
Department of Molecular and Cellular Biology, The University of Arizona, Life Sciences South Building, Tucson, Arizona 85721, USA.
George
G N
GN
Pickering
I J
IJ
Madden
S
S
Prince
R C
RC
Yu
E Y
EY
Denton
M B
MB
Younis
H S
HS
Aposhian
H V
HV
D000818:Animals; D004912:Erythrocytes / Q000378:metabolism; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D008658:Inactivation, Metabolic; D008297:Male; D008627:Mercuric Chloride / Q000037:antagonists & inhibitors* / Q000097:blood / Q000493:pharmacokinetics; D017669:Mercury Compounds / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification; D008958:Models, Molecular; D011817:Rabbits; D051381:Rats; D018036:Selenium Compounds / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification; D018038:Sodium Selenite / Q000037:antagonists & inhibitors* / Q000097:blood / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013052:Spectrometry, X-Ray Emission; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
D017669:Mercury Compounds; D018036:Selenium Compounds; C032901:mercury-selenium complex; D008627:Mercuric Chloride; D013455:Sulfur; D005978:Glutathione; D018038:Sodium Selenite