It has been claimed that Cu-Ca EDTA releases the Cu slowly into the bl
ood when injected as a therapeutic agent for Cu deficiency, but when o
verdosing occurs, animals may die in a few hours after the injection,
suggesting that Cu release is faster than expected. A total of 30 rats
were divided into six equal groups and injected with Cu-Ca EDTA at 4,
6, 13, 33 or 64 mg/kg body weight, the sixth group acted as control.
All rats were sacrificed 24 h later, with the exception of rats from g
roups 33 and 64 that died 7 and 2 h postinjection respectively. The ra
te of Cu transference to the liver increased linearly with the dose, f
rom (X +/- S.E.) 14.88 +/- 3.14 in group 4, to 134.47 +/- 21.86 mu g/h
in group 64. Injected animals developed liver and kidney degeneration
, hemorrhage and necrosis, which increased in severity with the Cu dos
e. Liver Cu accumulation was highest for group 13 (866.8 +/- 84.23 ppm
DM), while in group 64 reached only 167.0 +/- 14.99 ppm. It is conclu
ded that during acute Cu poisoning, the rate of transfer is responsibl
e for the liver and kidney damage, rather than the total amount of tra
nsferred Cu to those organs, as it is the case in chronic Cu poisoning
. The high rate of Cu transfer possibly surpasses the intrinsic mechan
isms of Cu deposition and free Cu is left into the cell with the devel
opment of necrosis. (C) 1997 Elsevier Science Ireland Ltd.