Trace metal interactions in vivo: inorganic cobalt enhances urinary copper excretion without producing an associated zincuresis in rats.

Overview

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.