Partitioning of renal zinc between metallothionein and ethylenediaminetetraacetic acid (EDTA) after treatment of rats with Ca(Na)2EDTA.
Calcium disodium edtate (EDTA) is a widely used chelator in the treatment of lead poisoning, although it also mobilizes other trace metals such as zinc. We have found that daily injection of 400 mg EDTA/kg body wt ip to rats results in an increase in the concentration of zinc (Zn) in the kidney when measured by atomic absorption spectroscopy. This increase is not associated with an induction of metallothionein (MT), a protein normally involved in the homeostasis of zinc. In fact, separation of kidney homogenate on a column of Sephadex G-75 demonstrates that virtually no Zn-MT remains in the kidney 24 hr after an EDTA injection, although after 3 days, Zn-MT levels appear to return to normal. Instead, increased renal Zn is found associated with residual EDTA. False high measurements of MT can be obtained from the Cd-saturation/hemoglobin assay due to the presence of residual EDTA in the kidney. Although nearly all of an injected dose of radiolabeled EDTA is rapidly excreted, 0.2 to 0.1% is retained in the kidney 1 day later; this is sufficient to account for the additional Zn. We propose that the small proportion of EDTA incorporated by pinocytosis into lysosomes in the renal cortical cells binds with all free Zn and subsequently depletes the MT concentration. Although the concentration of Zn measured in the kidney is elevated, there is actually less available for Zn-dependent activity.
D000818:Animals; D002104:Cadmium / Q000378:metabolism; D004492:Edetic Acid / Q000378:metabolism* / Q000652:urine; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D051381:Rats; D015032:Zinc / Q000378:metabolism*
D002104:Cadmium; D008668:Metallothionein; D004492:Edetic Acid; D015032:Zinc