Dose dependent changes in 74As-arsenate metabolism of Flemish Giant rabbits.
The metabolic handling of 74As-arsenate (As(V)) was studied in rabbits injected intraperitoneally (i.p.) with increasing doses of As(V) (0.00 to 1.00 mg As(V)/kg/day) over a period of 10 days. Plasma, packed cells, urine from the bladder and several tissues were analyzed for their 74As content and presence of 74As-As(V) metabolites 4 h after administration of 74As-As(V). 74As showed strong increases with increasing As(V) dose in nails and bone whereas in fat, thyroid and kidneys it decreased. Also with increasing As(V) dose, arsenate was less efficiently methylated to dimethylarsenic acid (DMA) and became more bound to insoluble tissue constituents. As a result 74As-DMA levels in tissues were systematically lower in the groups of rabbits receiving the higher doses, be it with a wide variation from one type of tissue to the other. The behaviour of 74As-monomethylarsonic acid (MMA) was different. The levels did not decrease significantly, occasionally even increased compared to the control group, indicating that especially the second methylation step is sensitive towards increasing doses of As(V). 74As-arsenite (As(III)), formed by in vivo reduction of As(V), reached maximal levels in the 0.25 mg As(V)/kg/day group as a result of the inhibited methylation. At doses > 0.25 mg As(V)/kg/day the amount of 74As-As(V) increased especially in plasma, packed cells and the urine in the bladder, indicative for a less efficient reduction of As(V).
De Kimpe
J
J
Laboratory for Analytical Chemistry, University of Gent, Belgium.
Cornelis
R
R
Wittevrongel
L
L
Vanholder
R
R
D000818:Animals; D001149:Arsenates / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001152:Arsenicals / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008745:Methylation; D011485:Protein Binding; D011817:Rabbits
D001149:Arsenates; D001152:Arsenicals; C020300:monomethylarsonic acid; C025657:arsenic acid