Cadmium-metallothionein-induced nephropathy

Abstract

Cadmium-metallothionein (Cd-Mt) was isolated from livers of rats repeatedly injected with small doses of cadmium (0.6 mg Cd/kg). Intraperitoneal injection of isolated Cd-Mt to control rats (1.2 mg Cd/kg) resulted in accumulation of a large percentage of the injected cadmium in the kidney (about 60 to 70%), whereas most Cd from the ip injection of a similar dose of CdCl 2 was recovered from the liver. The intracellular partitioning of Cd, whether given as Cd-Mt or CdCl 2, was similar. Cd given as CdCl 2 was bound to large molecular weight proteins isolated from cytoplasm 4 hr after Cd injections; Cd given as Cd-Mt was isolated as Cd-Mt. Changes in the morphology of renal tubular cells are observed both by light and electron microscopy in these rats within 4 hr after Cd-Mt injection. Necrosis of proximal renal tubular lining cells was observed within 24 hr. No ultrastructural changes were found in renal tubular cells after CdCl 2 injection. These studies demonstrate that the circulating Cd-Mt complex was nephrotoxic. It may also have a major role in the pathogenesis of Cd-induced renal disease following long-term exposure to cadmium.