74As-arsenate metabolism in Flemish Giant rabbits with renal insufficiency.

The metabolic management of carrier-free 74As-arsenate (As(V)) by uremic rabbits of the strain Flemish Giant was studied. Renal insufficiency was induced by nephrectomy of respectively 1 kidney (3/6 nephrectomy) and 1 kidney + 2/3 remaining kidney (5/6 nephrectomy). Marginal renal insufficiency developed in the 3/6 nephrectomized group, while animals of the 5/6 group became severely uremic. Renal excretion of 74As was reduced by 90% in 5/6 nephrectomized animals 4 h after intraperitoneal injection (i.p.) of the animals. The associated uremic syndrome caused a strong decrease in methylation capacity of inorganic arsenic (Asi). The second methylation step from monomethylarsonic acid (MMA) to dimethylarsinic acid (DMA) was more strongly affected than the first one, from arsenite (As(III)) to MMA. The increased availability of Asi led to more extensive binding to insoluble tissue constituents after 5/6 nephrectomy. The decreased renal reduction of As(V) led to a decrease in As(III) and an increase of As(V) and the associated As(V)-transferrin binding in plasma. Uptake of 74As-transferrin by the bone marrow might contribute to uremic anemia.