TY - JOUR
T1 - Observation of the seleno bis-(S-glutathionyl) arsinium anion in rat bile
AU - George, Graham N.
AU - Gailer, Jürgen
AU - Ponomarenko, Olena
AU - La Porte, Paul F.
AU - Strait, Karen
AU - Alauddin, Mohammad
AU - Ahsan, Habibul
AU - Ahmed, Selim
AU - Spallholz, Julian
AU - Pickering, Ingrid J.
N1 - Funding Information:
The authors thank the staff of the Stanford Synchrotron Radiation Lightsource (SSRL) for their assistance with XAS measurements. O.P. is an Associate in the Canadian Institutes of Health Research (CIHR) Training grant in Health Research Using Synchrotron Techniques (CIHR-THRUST). G.N.G. and I.J.P. are supported by Canada Research Chair awards. This work was supported by the CIHR (G.N.G., I.J.P.), the Saskatchewan Health Research Foundation (G.N.G., I.J.P.), the University of Saskatchewan , the Government of Saskatchewan (I.J.P.) and a Natural Sciences and Engineering Research Council of Canada Discovery Grant award (I.J.P. and J.G.). Use of SSRL, SLAC National Accelerator Laboratory, is supported by the U.S. DOE, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515 . The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research , and by the National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS) (including P41GM103393 ). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH.
Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Certain arsenic and selenium compounds show a remarkable mutual cancelation of toxicities, where a lethal dose of one can be voided by an equimolar and otherwise lethal dose of the other. It is now well established that the molecular basis of this antagonism is the formation and biliary excretion of seleno bis-(S-glutathionyl) arsinium anion [(GS)2AsSe]-. Previous work has definitively demonstrated the presence of [(GS)2AsSe]- in rabbit bile, but only in the presence of other arsenic and selenium species. Rabbits have a gall bladder, which concentrates bile and lowers its pH; it seems likely that this may be responsible for the breakdown of biliary [(GS)2AsSe]-. Since rats have no gall bladder, the bile proceeds directly through the bile duct from the hepatobiliary tree. In the present work we have shown that the primary product of biliary co-excretion of arsenic and selenium in rats is [(GS)2AsSe]-, with essentially 100% of the arsenic and selenium present as this species. The chemical plausibility of the X-ray absorption spectroscopy-derived structural conclusions of this novel arsenic and selenium co-excretion product is supported by density functional theory calculations. These results establish the biomolecular basis to further explore the use of selenium dietary supplements as a possible palliative for chronic low-level arsenic poisoning of human populations.
AB - Certain arsenic and selenium compounds show a remarkable mutual cancelation of toxicities, where a lethal dose of one can be voided by an equimolar and otherwise lethal dose of the other. It is now well established that the molecular basis of this antagonism is the formation and biliary excretion of seleno bis-(S-glutathionyl) arsinium anion [(GS)2AsSe]-. Previous work has definitively demonstrated the presence of [(GS)2AsSe]- in rabbit bile, but only in the presence of other arsenic and selenium species. Rabbits have a gall bladder, which concentrates bile and lowers its pH; it seems likely that this may be responsible for the breakdown of biliary [(GS)2AsSe]-. Since rats have no gall bladder, the bile proceeds directly through the bile duct from the hepatobiliary tree. In the present work we have shown that the primary product of biliary co-excretion of arsenic and selenium in rats is [(GS)2AsSe]-, with essentially 100% of the arsenic and selenium present as this species. The chemical plausibility of the X-ray absorption spectroscopy-derived structural conclusions of this novel arsenic and selenium co-excretion product is supported by density functional theory calculations. These results establish the biomolecular basis to further explore the use of selenium dietary supplements as a possible palliative for chronic low-level arsenic poisoning of human populations.
KW - Arsenic-selenium antagonism
KW - DFT
KW - EXAFS
KW - X-ray absorption spectroscopy
UR - http://www.scopus.com/inward/record.url?scp=84957899693&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2016.01.022
DO - 10.1016/j.jinorgbio.2016.01.022
M3 - Article
C2 - 26883676
AN - SCOPUS:84957899693
VL - 158
SP - 24
EP - 29
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
SN - 0162-0134
ER -