Kidney synthesizes less metallothionein than liver in response to cadmium chloride and cadmium-metallothionein.
Acute exposure to Cd produces liver injury, whereas chronic exposure results in kidney injury. Tolerance to the hepatotoxicity is observed during chronic exposure to Cd due to the induction of metallothionein (MT). The nephrotoxicity produced by chronic Cd exposure purportedly results from renal uptake of Cd-metallothionein (CdMT) synthesized in liver. The change in target organ from liver to kidney might be due to a lower amount of MT synthesized in the kidney in response to CdMT. Therefore, the purpose of the present study was to quantitate hepatic and renal MT induced by CdCl2 and CdMT. MT levels in mice were quantitated using the Cd-heme assay 24 hr after administration of CdCl2 (0.5-3.0 mg Cd/kg) and CdMT (0.1-0.5 mg Cd/kg). In both liver and kidney, MT reached higher levels following administration of CdCl2 (220 and 60 micrograms/g, respectively) than of CdMT (25 and 35 micrograms/g, respectively), probably because higher dosages of CdCl2 than CdMT are tolerated. CdMT produced 19 and 3 micrograms MT/micrograms Cd in liver and kidney, respectively, while CdCl2 produced 11 and 6 micrograms MT/micrograms Cd, respectively. In conclusion, induction of MT occurs in both the liver and kidney after administration of CdCl2 and CdMT. However, the kidney is less responsive than the liver to the induction of MT by both forms of Cd, which may contribute to making the kidney the target organ of toxicity during chronic Cd exposure.
Sendelbach
L E
LE
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Klaassen
C D
CD
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride; D003609:Dactinomycin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000493:pharmacokinetics* / Q000633:toxicity; D051379:Mice; D051381:Rats
C004203:cadmium-binding protein; D002104:Cadmium; D003609:Dactinomycin; D008668:Metallothionein; D019256:Cadmium Chloride