TY - JOUR
T1 - Selenium-mediated arsenic excretion in mammals
T2 - A synchrotron-based study of whole-body distribution and tissue-specific chemistry
AU - Ponomarenko, Olena
AU - La Porte, Paul F.
AU - Singh, Satya P.
AU - Langan, George
AU - Fleming, David E.B.
AU - Spallholz, Julian E.
AU - Alauddin, Mohammad
AU - Ahsan, Habibul
AU - Ahmed, Selim
AU - Gailer, Jürgen
AU - George, Graham N.
AU - Pickering, Ingrid J.
N1 - Funding Information:
We thank T. C. MacDonald, M. Gallego-Gallegos, M. J. Hackett, N. V. Dolgova, K. H. Nienaber, A. K. James and S. Nehzati for assistance in XFI and XAS experiments. Work at the University of Saskatchewan was funded by awards from the Canadian Institutes of Health Research (CIHR) (FRN68849 to G. N. G. and I. J. P.), the Natural Sciences and Engineering Research Council of Canada (NSERC) (RGPIN 04632-2014 to G. N. G. and RGPIN 05810-2016 to I. J. P.), by the Government of Saskatchewan Innovation and Science Fund (to I. J. P.) and by the Canada Foundation for Innovation (to I. J. P.). G. N. G. and I. J. P. are Canada Research Chairs. O. P. is a Research Associate in the CIHR Training grant in Health Research Using Synchrotron Techniques (CIHR-THRUST). J. E. S. and P. F. L. P. acknowledge grant support from the National Cancer Institute/National Institutes of Health (NIH) (grant 1R21CA117111-01) and American Cancer Society (grant ROG-06-098-01). Work at the University of Chicago was funded by the NIH (R01CA107432 and R01CA102484 to HA). Work at Mount Allison University was funded by NSERC (RGPIN-261523 to D. E. B. F.). Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, 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 NIH, National Institute of General Medical Sciences (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:
© 2017 The Royal Society of Chemistry.
PY - 2017/11
Y1 - 2017/11
N2 - Arsenicosis, a syndrome caused by ingestion of arsenic contaminated drinking water, currently affects millions of people in South-East Asia and elsewhere. Previous animal studies revealed that the toxicity of arsenite essentially can be abolished if selenium is co-administered as selenite. Although subsequent studies have provided some insight into the biomolecular basis of this striking antagonism, many details of the biochemical pathways that ultimately result in the detoxification and excretion of arsenic using selenium supplements have yet to be thoroughly studied. To this end and in conjunction with the recent Phase III clinical trial "Selenium in the Treatment of Arsenic Toxicity and Cancers", we have applied synchrotron X-ray techniques to elucidate the mechanisms of this arsenic-selenium antagonism at the tissue and organ levels using an animal model. X-ray fluorescence imaging (XFI) of cryo-dried whole-body sections of laboratory hamsters that had been injected with arsenite, selenite, or both chemical species, provided insight into the distribution of both metalloids 30 minutes after treatment. Co-treated animals showed strong co-localization of arsenic and selenium in the liver, gall bladder and small intestine. X-ray absorption spectroscopy (XAS) of freshly frozen organs of co-treated animals revealed the presence in liver tissues of the seleno bis-(S-glutathionyl) arsinium ion, which was rapidly excreted via bile into the intestinal tract. These results firmly support the previously postulated hepatobiliary excretion of the seleno bis-(S-glutathionyl) arsinium ion by providing the first data pertaining to organs of whole animals.
AB - Arsenicosis, a syndrome caused by ingestion of arsenic contaminated drinking water, currently affects millions of people in South-East Asia and elsewhere. Previous animal studies revealed that the toxicity of arsenite essentially can be abolished if selenium is co-administered as selenite. Although subsequent studies have provided some insight into the biomolecular basis of this striking antagonism, many details of the biochemical pathways that ultimately result in the detoxification and excretion of arsenic using selenium supplements have yet to be thoroughly studied. To this end and in conjunction with the recent Phase III clinical trial "Selenium in the Treatment of Arsenic Toxicity and Cancers", we have applied synchrotron X-ray techniques to elucidate the mechanisms of this arsenic-selenium antagonism at the tissue and organ levels using an animal model. X-ray fluorescence imaging (XFI) of cryo-dried whole-body sections of laboratory hamsters that had been injected with arsenite, selenite, or both chemical species, provided insight into the distribution of both metalloids 30 minutes after treatment. Co-treated animals showed strong co-localization of arsenic and selenium in the liver, gall bladder and small intestine. X-ray absorption spectroscopy (XAS) of freshly frozen organs of co-treated animals revealed the presence in liver tissues of the seleno bis-(S-glutathionyl) arsinium ion, which was rapidly excreted via bile into the intestinal tract. These results firmly support the previously postulated hepatobiliary excretion of the seleno bis-(S-glutathionyl) arsinium ion by providing the first data pertaining to organs of whole animals.
UR - http://www.scopus.com/inward/record.url?scp=85034437596&partnerID=8YFLogxK
U2 - 10.1039/c7mt00201g
DO - 10.1039/c7mt00201g
M3 - Article
C2 - 29058732
AN - SCOPUS:85034437596
VL - 9
SP - 1585
EP - 1595
JO - Metallomics
JF - Metallomics
SN - 1756-5901
IS - 11
ER -