Induction of renal metallothionein synthesis by parenteral cadmium-thionein in rats

Abstract

Cadmium-thionein (Cd-Th) was isolated from livers of rats repeatedly treated with small doses of cadmium chloride. A major portion (55 per cent) of intraperitoneally injected Cd-Th was deposited in the kidney followed by renal damage. Subcellular fractionation of kidney homogenate at 1, 4, 24 and 48 hr after Cd-Th injection revealed that only less than 7 per cent of the cadmium war, accumulated in the lysosomal fraction and more than 50 per cent of cadmium was recovered from the cytosol. Injection of [ 35S]cysteine into rats pre-injected with sublethal doses of Cd-Th resulted in the incorporation of radioactivity into newly synthesized thionein in the kidney between 4 and 24 hr. A major portion of the renal cadmium was bound to metallothionein at all time intervals studied. These studies demonstrated that the Cd-Th complex in the processes of entering the renal cells intact produces cell injury. The thionein moiety of the injected Cd-Th is degraded and resynthesized in the kidney, while nearly all of the metal ( > 90 per cent) is always bound to thionein. The role of the lysosomal system in the renal toxicity of Cd-Th is minimal.