Roles of Metallothionein and Glutathione in Cadmium Toxicity

The sequestration of cadmium by MT is a double-edged sword, i.e., although Cd-MT is relatively inert when stored as an intracellular complex, it becomes a potent nephrotoxicant after reaching the systemic circulation (Cherian et al. 1976 Squibb et al. 1984). Human cadmium nephrotoxicity may be related to Cd-MT exposure, because this may be a major form of cadmium in diet (Maitani et al. 1984). Cadmium salts absorbed from the GI tract or lungs are initially transported to liver, where synthesis of MT is induced. Continual exposure to cadmium results in liver injury with leakage of Cd-MT into the systemic circulation (Dudley et al. 1985). The complex is transported to kidney, filtered, and reabsorbed by the proximal tubule, possibly via a mechanism involving receptor mediated endocytosis (Foulkes 

1978 Squibb et al. 1984 Dudley et al. 1985 Dorian et al. 1992). The reabsorbed complex is degraded by lysosomal enzymes, and the released cadmium ion induces MT in proximal tubule cells. Eventually, the capacity to synthesize MT is exceeded, and cadmium can poison sensitive molecular targets. 

The effects of cadmium on experimental animals and humans involve multiple organ systems and many mechanisms have been presented to explain these effects. Due to continued mobilization of cadmium in the 

This article does not represent or contain official policy statements of the Food and Drug Administration. 

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