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Title: Intracellular metabolism and effects of circulating cadmium-metallothionein in the kidney

Journal Article · · Environ. Health Perspect.; (United States)
DOI:https://doi.org/10.1289/ehp.845431· OSTI ID:5975454

The mechanism of cadmium-metallothionein (CdMT)-mediated nephrotoxicity is being studied in rats using an acute dose regimen. Results of metabolism studies have shown that injected CdMT is rapidly degraded by the kidney with the release of Cd/sup 2 +/ into the cell cytoplasm. Ultrastructural studies indicate that an increase in the number of small lysosomes is the first measurable effect of CdMT in the kidney at 1 hr. This is followed by an increase in the number of small vesicles at 4 hr. It is proposed that these effects are the result of decreased primary lysosome formation and an inhibition of the fusion of pinocytotic vesicles with cell lysosomes by Cd. Functional alterations measured 8 hr after CdMT injection include an increase in urine volume and increased excretion of the low molecular weight protein, RNAase. Prior induction of renal MT by Zn pretreatment prevents the induction of polyuria and low molecular weight proteinuria by CdMT. These data provide further evidence that CdMT nephrotoxicity occurs as a result of Cd/sup 2 +/ toxicity within the cell. 25 references, 3 figures.

Research Organization:
National Institute of Environmental Health Sciences, Research Triangle Park, NC
OSTI ID:
5975454
Journal Information:
Environ. Health Perspect.; (United States), Vol. 54
Country of Publication:
United States
Language:
English