J. Dekimpe et al., BASAL-METABOLISM OF INTRAPERITONEALLY INJECTED CARRIER-FREE AS-74-LABELED ARSENATE IN RABBITS, Fundamental and applied toxicology, 34(2), 1996, pp. 240-248
The time-dependent occurrence of [As-74]arsenate metabolites in Flemis
h Giant rabbits was investigated. As absorbed rapidly, reaching maxima
l concentrations in plasma and packed cells after 30 min and 2 hr, res
pectively. The [As-74]arsenate in plasma and packed cells was reduced
to [As-74]arsenite, to 35 and 50% of the total As-74, respectively. Th
e concentration of methylated As species in plasma and packed cells in
creased rapidly after 30 min. About 18% of total plasma As-74 maximall
y bound to transferrin. Two-thirds of total As-74 in packed cells boun
d to hemoglobin. Whereas little or no [As-74]monomethylarsonic acid, o
ne of the main As metabolites in humans, could be found in other anima
ls, it is present in measurable amounts in the Flemish Giant. Furtherm
ore, the plasma clearance rate of As-74 species is lower than that in
other rabbits and more similar to that of humans. The tissue As-74 dis
tribution varied widely with the highest concentrations in kidneys, li
ver, and lungs. As-74 accumulated in bone whereas other tissues and bl
ood showed rapid clearance rates. In muscle and heart an important par
t of arsenic was associated with components insoluble in phosphate-buf
fered isotonic saline. Binding of arsenic to soluble tissue proteins w
as most important in the kidneys, liver, and spleen. [As-74]Arsenate m
etabolites were detected in all tissues. The relative amounts of [As-7
4]arsenite or [As-74]monomethylarsonic acid seldom exceeded 15% of tot
al tissue As-74. The proportion of [As-74]dimethylarsenic acid in the
low molecular As-74 fraction increased steadily. Substantial amounts o
f [As-74]monomethylarsonic acid were found in the tissues. (C) 1996 So
ciety of Toxicology.