TY - JOUR
T1 - The seleno bis(S-glutathionyl) arsinium ion is assembled in erythrocyte lysate
AU - Manley, Shawn A.
AU - George, Graham N.
AU - Pickering, Ingrid J.
AU - Glass, Richard S.
AU - Prenner, Elmar J.
AU - Yamdagni, Raghav
AU - Wu, Qiao
AU - Gailer, Jürgen
PY - 2006/4
Y1 - 2006/4
N2 - Approximately 75 million people are currently exposed to arsenic concentrations in drinking water, which is associated with the development of internal cancers. One way to ameliorate this undesirable situation is to remove arsenic (arsenite and arsenate) from drinking water. An alternative approach is the development of an inexpensive palliative dietary supplement that promotes the excretion of intestinally absorbed arsenite from the body. To this end, the simultaneous administration of New Zealand white rabbits with arsenite and selenite resulted in the biliary excretion of the seleno-bis (S-glutathionyl) arsinium ion, [(GS)2AsSe]-. This apparent detoxification mechanism has been recently extended to environmentally relevant doses [Gailer, J., Ruprecht, L., Reitmeir, P., Benker, B., and Schramel, P. (2004) Appl. Organometal. Chem. 18, 670-675]. The site of formation of this excretory product in the organism, however, is unknown. To investigate if [(GS) 2AsSe]- is formed in rabbit blood, we added arsenite and selenite and analyzed blood aliquots using arsenic and selenium X-ray absorption spectroscopy. The characteristic arsenic and selenium X-ray absorption spectra of [(GS)2AsSe]- were detected within 2 min after addition and comprised 95% of the blood selenium 30 min after addition. To elucidate if erythrocytes are involved in the biosynthesis of [(GS)2AsSe] - in blood, arsenite and 77Se-selenite were added to rabbit erythrocyte lysate and the obtained solution was analyzed by 77Se NMR spectroscopy (273 K). This resulted in a 77Se NMR signal with a chemical shift identical to that of synthetic [(GS) 2AsSe]- added to lysate. Combined, these results demonstrate that [(GS)2AsSe]- is rapidly formed in blood and that erythrocytes are an important site for the in vivo formation of this toxicologically important metabolite.
AB - Approximately 75 million people are currently exposed to arsenic concentrations in drinking water, which is associated with the development of internal cancers. One way to ameliorate this undesirable situation is to remove arsenic (arsenite and arsenate) from drinking water. An alternative approach is the development of an inexpensive palliative dietary supplement that promotes the excretion of intestinally absorbed arsenite from the body. To this end, the simultaneous administration of New Zealand white rabbits with arsenite and selenite resulted in the biliary excretion of the seleno-bis (S-glutathionyl) arsinium ion, [(GS)2AsSe]-. This apparent detoxification mechanism has been recently extended to environmentally relevant doses [Gailer, J., Ruprecht, L., Reitmeir, P., Benker, B., and Schramel, P. (2004) Appl. Organometal. Chem. 18, 670-675]. The site of formation of this excretory product in the organism, however, is unknown. To investigate if [(GS) 2AsSe]- is formed in rabbit blood, we added arsenite and selenite and analyzed blood aliquots using arsenic and selenium X-ray absorption spectroscopy. The characteristic arsenic and selenium X-ray absorption spectra of [(GS)2AsSe]- were detected within 2 min after addition and comprised 95% of the blood selenium 30 min after addition. To elucidate if erythrocytes are involved in the biosynthesis of [(GS)2AsSe] - in blood, arsenite and 77Se-selenite were added to rabbit erythrocyte lysate and the obtained solution was analyzed by 77Se NMR spectroscopy (273 K). This resulted in a 77Se NMR signal with a chemical shift identical to that of synthetic [(GS) 2AsSe]- added to lysate. Combined, these results demonstrate that [(GS)2AsSe]- is rapidly formed in blood and that erythrocytes are an important site for the in vivo formation of this toxicologically important metabolite.
UR - http://www.scopus.com/inward/record.url?scp=33646113384&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646113384&partnerID=8YFLogxK
U2 - 10.1021/tx0503505
DO - 10.1021/tx0503505
M3 - Article
C2 - 16608173
AN - SCOPUS:33646113384
SN - 0893-228X
VL - 19
SP - 601
EP - 607
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 4
ER -