Gold(I) efflux from auranofin-treated red blood cells. Evidence for a glutathione-gold-albumin metabolite.
The efflux of gold from red blood cells (RBCs) exposed to 10-100 microM auranofin [the second generation chrysotherapy agent, triethylphosphine-(2,3,4,6-tetra-O-acetyl-1-beta-D-glucopyranosato -S-)gold(I)] was studied. RBCs in whole blood were allowed to accumulate gold, and then were placed in fresh plasma or buffered saline solution. In plasma, the kinetics of efflux were first order in gold with an apparent rate constant of 0.81 +/- 0.18 hr-1. Serum albumin, in plasma or added to a buffered solution, shifted the equilibrium between intra- and extracellular gold in favor of the latter (compared to saline solution). [14C]Glutathione, generated by in situ labeling, also effluxed and associated with the albumin and gold, providing the first direct evidence that the albumin-gold-glutathione complex (AlbSAuSG) may be a circulating metabolite of auranofin formed after both of the original ligands of auranofin are displaced.
Department of Chemistry, University of Wisconsin-Milwaukee 53201.
C F
CF
Shaw
A A
AA
Isab
M T
MT
Coffer
C K
CK
Mirabelli
D000418:Albumins / Q000378:metabolism*; D001310:Auranofin / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D002478:Cells, Cultured; D002850:Chromatography, Gel; D004912:Erythrocytes / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006046:Gold / Q000378:metabolism*; D006801:Humans; D007700:Kinetics
D000418:Albumins; D001310:Auranofin; D006046:Gold; D005978:Glutathione