Minimal role of metallothionein in decreased chelator efficacy for cadmium.
Chelator efficacy in Cd poisoning drops precipitously if therapy is not commenced almost immediately after exposure. Metallothionein (MT), a low-molecular-weight metal-binding protein with high affinity for Cd, may be important for this phenomenon. To more fully assess this role of MT in the acute drop in chelator efficacy following Cd poisoning, rats were injected iv with radioisotopic Cd (1mg/kg as CdCl2; 50 muCi/kg) followed by diethylenetriaminepentaacetic acid (DTPA; 90 mg/kg ip) at various times (0, 15, 30, 60, and 120 min) after Cd. Ther percentage of the Cd dose remaining in major organs 24 hr following Cd was determined. Although DTPA reduced Cd content in the various organs when given immediately after Cd, the chelator was ineffective at all later times. Increases in hepatic and renal MT did not occur until 2 hr after Cd, and did not coincide with the earlier drop in chelator efficacy. Blockade of MT synthesis by actinomycin D treatment (1.25 mg/kg, 1 hr before Cd) failed to prolong the chelators effectiveness. Furthermore, newborn rats have high levels of hepatic MT which had no effect on the time course of chelator effectiveness since DTPA still decreased Cd organ contents if given immediately following Cd but had no effect if given 2 hr after Cd. Therefore, if appears that MT does not have an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The quick onset of chelator ineffectiveness may be due to the rapid uptake of Cd into tissues which makes it relatively unavailable of chelation.
D000818:Animals; D002104:Cadmium / Q000302:isolation & purification / Q000378:metabolism; D002105:Cadmium Poisoning; D002614:Chelating Agents / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008667:Metalloproteins / Q000378:metabolism*; D008668:Metallothionein / Q000096:biosynthesis / Q000378:metabolism*; D004369:Pentetic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002614:Chelating Agents; D008667:Metalloproteins; D002104:Cadmium; D003609:Dactinomycin; D004369:Pentetic Acid; D008668:Metallothionein