Basal metabolism of intraperitoneally injected carrier-free 74As-labeled arsenate in rabbits.
The time-dependent occurrence of [74As]arsenate metabolites in Flemish Giant rabbits was investigated. As absorbed rapidly, reaching maximal concentrations in plasma and packed cells after 30 min and 2 hr, respectively. The [74As]arsenate in plasma and packed cells was reduced to [74As]arsenite, to 35 and 50% of the total 74As, respectively. The concentration of methylated As species in plasma and packed cells increased rapidly after 30 min. About 18% of total plasma 74As maximally bound to transferrin. Two-thirds of total 74As in packed cells bound to hemoglobin. Whereas little or no [74As]monomethylarsonic acid, one of the main As metabolites in humans, could be found in other animals, it is present in measurable amounts in the Flemish Giant. Furthermore, the plasma clearance rate of 74As species is lower than that in other rabbits and more similar to that of humans. The tissue 74As distribution varied widely with the highest concentrations in kidneys, liver, and lungs. 74As accumulated in bone whereas other tissues and blood showed rapid clearance rates. In muscle and heart an important part of arsenic was associated with components insoluble in phosphate-buffered isotonic saline. Binding of arsenic to soluble tissue proteins was most important in the kidneys, liver, and spleen. [74As]Arsenate metabolites were detected in all tissues. The relative amounts of [74As]arsenite or [74As]monomethylarsonic acid seldom exceeded 15% of total tissue 74As. The proportion of [74As]dimethylarsenic acid in the low molecular 74As fraction increased steadily. Substantial amounts of [74As]monomethylarsonic acid were found in the tissues..
Kimpe
J D
JD
Laboratory for Analytical Chemistry, Institute for Nuclear Sciences, University of Gent, Proeftuinstraat 86, Gent, B-9000, Belgium. Cornelis@inwchem.rug.ac.be
Cornelis
R
R
Mees
L
L
Vanholder
R
R
D000818:Animals; D001149:Arsenates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001151:Arsenic; D001481:Basal Metabolism / Q000187:drug effects*; D006207:Half-Life; D007274:Injections, Intraperitoneal; D008297:Male; D008745:Methylation; D011485:Protein Binding; D011817:Rabbits; D011868:Radioisotopes; D014018:Tissue Distribution
D001149:Arsenates; D011868:Radioisotopes; D001151:Arsenic