Trace metal interactions in vivo: inorganic cobalt enhances urinary copper excretion without producing an associated zincuresis in rats.
The effects of cobalt chloride on copper and zinc metabolism in male Sprague-Dawley rats were examined. These effects were compared with those of penicillamine, a chelating agent utilized in the therapy of the genetic abnormality of copper metabolism in humans, Wilson's disease. Cobalt elicited an increased (approximately 4-fold) urinary excretion of copper lasting through 72 h following a single cobalt dose. In contrast to the marked increase in urinary zinc excretion produced by penicillamine, cobalt greatly reduced (approximately 75%) zinc output in urine. Tissue copper and zinc concentrations were measured after treatment with cobalt at doses ranging from 12 to 60 mg/kg body weight. Substantially reduced (approximately 25%) renal copper concentration was observed at 1 and 3 d after cobalt administration. In addition, cobalt produced a concurrent dose-dependent elevation (up to 1.6-fold) in hepatic zinc concentration. Cytosolic zinc was eluted from a Sephadex G-75 column in the molecular weight region associated with metallothionein. Time-dependent induction of metallothionein concentration (10-fold) in liver by cobalt was confirmed by the cadmium/hemoglobin affinity assay. The ability of inorganic cobalt to elevate zinc concentration in liver and produce increased urinary copper excretion without the zincuresis that normally accompanies penicillamine administration represents a newly defined biological property of this essential trace metal.
Rosenberg
D W
DW
Rockefeller University Hospital, New York, NY 10021.
Kappas
A
A
D000818:Animals; D003035:Cobalt / Q000008:administration & dosage / Q000494:pharmacology*; D003300:Copper / Q000493:pharmacokinetics / Q000652:urine*; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010396:Penicillamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D015032:Zinc / Q000493:pharmacokinetics / Q000652:urine*
D003035:Cobalt; D003300:Copper; D010396:Penicillamine; D015032:Zinc