Observation of the seleno bis-(S-glutathionyl) arsinium anion in rat bile

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. X-ray absorption spectroscopy and density functional theory characterization of the biliary co-excretory product the seleno-bis-S-glutathionyl arsinium ion. [Display omitted] •X-ray absorption spectroscopy (XAS) and density functional theory (DFT) are utilized•The arsenic and selenium biliary co-excretory product characterized with XAS and DFT•Rat bile contains essentially 100% of the arsenic selenium species.•XAS indicates a trivalent arsenic species bound to selenide.•Se K-edge XAS shows hydrogen bonding to water.