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.