The comparative abilities of inorganic cobalt and cobalt-protoporphyrin to affect copper metabolism and elevate plasma ceruloplasmin.

A comparison of the effects of the trace element cobalt and the protoporphyrin chelate of this metal, cobalt-protoporphyrin, on copper and zinc metabolism in male Sprague-Dawley rats was made. Following subcutaneous treatment (250 mumol/kg body weight), inorganic cobalt elicited only a moderate (25-30%) and transient (48 h) increase in plasma copper levels and a concomitant elevation (up to 2-fold) in ceruloplasmin (ferroxidase) activity. Treatment with cobalt-protoporphyrin (25 mumol/kg), however, produced substantial (2- to 3-fold) and prolonged (up to 4 weeks) increases in plasma copper levels and ceruloplasmin. This effect on ceruloplasmin was specific to cobalt-protoporphyrin, since equimolar doses (25 mumol/kg body weight) of both tin-protoporphyrin and iron-protoporphyrin did not produce changes in the levels of circulating ceruloplasmin. Both inorganic cobalt and cobalt-protoporphyrin produced an elevation in liver cytosolic zinc levels at 48 h. This zinc associated with a fraction that coelutes with authentic metallothionein standard. These differential effects of inorganic cobalt and cobalt-protoporphyrin on copper and zinc metabolism represent newly defined biological properties of this trace element and point to the importance of chemical speciation as an underlying factor in the ultimate biological actions of metals.