title: Observation of the seleno bis-(S-glutathionyl) arsinium anion in rat bile.
abstract: 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.
authors.affiliation: Molecular and Environmental Science Research Group, Department of Geological Sciences, University of Saskatchewan, Saskatoon, SK S7N 5E2, Canada; Toxicology Center, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada; Department of Chemistry, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
authors.forename: Graham N
authors.initials: GN
authors.lastname: George
authors.affiliation: Department of Chemistry, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gailer
authors.affiliation: Molecular and Environmental Science Research Group, Department of Geological Sciences, University of Saskatchewan, Saskatoon, SK S7N 5E2, Canada.
authors.forename: Olena
authors.initials: O
authors.lastname: Ponomarenko
authors.affiliation: Division of Hematology-Oncology, University of California Los Angeles, CA, USA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: La Porte
authors.affiliation: School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Strait
authors.affiliation: Chemistry Department, Wagner College, Staten Island, NY, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Alauddin
authors.affiliation: Department of Health Sciences, The University of Chicago, Chicago, IL, USA.
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
authors.affiliation: School of Medicine, University Malaysia Sabah, Sabah, Malaysia.
authors.forename: Selim
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Nutritional Sciences, Texas Tech University, Lubbock, TX, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Spallholz
authors.affiliation: Molecular and Environmental Science Research Group, Department of Geological Sciences, University of Saskatchewan, Saskatoon, SK S7N 5E2, Canada; Toxicology Center, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada; Department of Chemistry, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
authors.forename: Ingrid J
authors.initials: IJ
authors.lastname: Pickering
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism*; D001151:Arsenic / Q000737:chemistry / Q000378:metabolism*; D001646:Bile / Q000378:metabolism*; D004336:Drug Antagonism; D008297:Male; D015394:Molecular Structure; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D018036:Selenium Compounds / Q000737:chemistry / Q000378:metabolism*; D056928:X-Ray Absorption Spectroscopy
chemical_list: D000838:Anions; D018036:Selenium Compounds; D001151:Arsenic
keywords: Arsenic–selenium antagonism; DFT; EXAFS; X-ray absorption spectroscopy