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Trace Metal Interactions in Vivo: Inorganic Cobalt Enhances Urinary Copper Excretion without Producing an Associated Zincuresis in Rats¹

The Rockefeller University Hospital, New York, NY 10021

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, Willson's disease. Cobalt elicited an increased (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 (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 (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.

KEY WORDS: • cobalt • copper • zinc • metallothionein • D-penicillamine • rat

¹ Supported in part by U.S. Public Health Service Grant ES-5-01055 and U.S. Public Health Service Clinical Nutrition Core Grant CA 29502, and a gift from the Eugene and Theresa Lang Foundation. Computerized data collection and statistical analysis for this study were accomplished using the CLINFO system funded by the National Institutes of Health, General Clinical Research Center Grant MO1 RR00102.

Manuscript received 13 December 1988. Revision accepted 8 May 1989.