Nephrotoxic impact of multiple short-interval cadmium-metallothionein injections in the rat

The cadmium-metallothionein (CdMT) injection model was used to examine whether multiple short-interval injections of CdMT, instead of a single dose, could better reproduce the features of chronic exposure to inorganic cadmium. Male Wistar rats were given an initial CdMT dose and four subsequent doses subcutaneously at 2-h intervals. A control group, given saline, was compared with a low dose group (0.2 + 4 x 0.1 mg Cd/kg b.w.) and high dose group (0.4 + 4 x 0.1 mg Cd/kg b.w.). Nephrotoxic effects were seen at the high dose. A marked proteinuria began 6-12 h after the first injection and extended to day 9. A progressive, unreversed calciuria appeared at 6 h and reached its maximum at day 13. This was a marked increase in duration compared with the transient peaks of proteinuria and calciuria observed in previous single dose studies. The unreversed calciuria and the marked proteinuria are suggestive of residual tubular damage, which may be irreversible. In conclusion, the model with multiple short-interval CdMT injections more closely reproduces the situation in long-term exposure to inorganic cadmium, compared to the single dose models previously employed.