Cadmium-metallothionein-induced nephrotoxicity

Thesis/Dissertation · Mon Dec 31 23:00:00 EST 1990

OSTI ID:5506075

Dorian, M D.C.

Kidney is the target organ of toxicity after chronic exposure to inorganic cadmium. The nephrotoxic effects can be reproduced by acute administration of cadmium bound to metallothionein (CdMT), a low-molecular-weight protein. The mechanisms of Cd-induced nephrotoxicity are not clearly understood. Therefore, to better comprehend the mechanisms responsible for the renal toxicity, several studies were conducted. The distribution of CdMT was determined after iv administration of [sup 109]CdMT and [[sup 35]S]-CdMT to mice. [sup 109]Cd concentration in the kidney remained unchanged for at least a week after the injection; in contrast, [[sup 35]S]-CdMT degradation occurred quickly. The intrarenal distribution of CdMT was then quantified by light microscopic autoradiography. After administration of [sup 109]CdMT and [[sup 35]S]-CdMT, [sup 109]Cd as well as [sup 35]S accumulated in the proximal convoluted tubules, the site of Cd nephrotoxicity. These results suggest that CdMT is reabsorbed by the proximal convoluted tubular cells as an intact complex of Cd and MT. The importance of the metal in the renal uptake of CdMT was determined by comparing [[sup 35]S]-CdMT and [[sup 35]S]-ZnMT disposition. Rapid renal uptake, degradation, and saturation of reabsorption were observed for both complexes. ZnMT protected against CdMT nephrotoxicity without decreasing the renal Cd concentration. Comparison of CdMT and CdCl[sub 2] uptake by light microscopic autoradiography demonstrated that CdMT preferentially concentrated in the proximal convoluted tubules and was nephrotoxic, whereas CdCl[sub 2] distributed equally to the proximal convoluted and straight tubules and was not nephrotoxic. Surprisingly, higher Cd concentrations were obtained in the proximal convoluted tubules of mice treated with CdCl[sub 2] than with CdMT. In conclusion, CdMT appears to be reabsorbed as a complex by the proximal convoluted tubular cells, the site of Cd-induced nephrotoxicity.

• Research Organization: Kansas State Univ., Manhattan, KS (United States)
• OSTI ID: 5506075
• Country of Publication: United States
• Language: English

Related Subjects

550500 -- Metabolism
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AUTORADIOGRAPHY
BIOLOGICAL ACCUMULATION
BODY
CADMIUM
CHRONIC EXPOSURE
CLEARANCE
ELEMENTS
EXCRETION
KIDNEYS
METALLOPROTEINS
METALLOTHIONEIN
METALS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RENAL CLEARANCE
TOXICITY
TUBULES
UPTAKE