The chronic toxicity of equine cadmium metallothionein in the rat.

The extensive renal tubular necrosis that results in male rats after the intravenous injection of a single, low dose of equine kidney cadmium (Cd), zinc(Zn)-metallothionein (MT) (0.2 mg MT-bound-Cd/kg body wt.) is followed within 72 h by active regeneration. With repeated administration of the same dose at 3- or 4-day intervals, lesion resolves although, at least initially, the kidney content of Cd increases progressively. At any time during treatment, about 40% of the accumulated Cd is bound as the endogenous (Cd, Cu)MT. The rate of increase in the renal Cd content is dependent on the ratio of Cd:Zn in the injected metalloprotein, and is appreciably less when the constant dose of protein-bound Cd is given as a (2.4 Cd:1 Zn)MT, than as a (3.0 Cd:1 Zn)MT. On repeated administration of the latter preparation, however, the concentration of Cd in the kidney does not attain a critical concentration, above which persistent tubular damage occurs, but reaches a maximum of about 150-160 micrograms Cd/g wet wt. (after 16 doses) and then declines. After 19 doses of the (2.4 Cd:1 Zn)MT under the same conditions, the renal Cd concentration is submaximal and is less (92 micrograms Cd/g wet wt.) than that after either 16 or 27 doses of the (3.0 Cd:1 Zn)MT. In animals that are dosed with either of the heterologous MT preparations, the first dose, although not innocuous, seems to protect the kidneys against further damage by subsequent doses. Repeated doses, however, lead to vascular changes, e.g. lymphoid infiltration, periarteriole oedema and dilation of the arcuate veins, and to dilation of the glomerular spaces.