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 protop orphyrin chelate of this metal, cobalt-protoporphyrin, on copper and z inc metabolism in male Sprague-Dawley rats was made. Following subcuta neous treatment (250 mu mol/kg body weight), inorganic cobalt elicited only a moderate (25-30%) and transient (48 h) increase in plasma copp er levels and a concomitant elevation (up to 2-fold) in ceruloplasmin (ferroxidase) activity. Treatment with cobalt-protoporphyrin (25 mu mo l/kg), however, produced substantial(2- to 3-fold) and prolonged (up t o 4 weeks) increases in plasma copper levels and ceruloplasmin. This e ffect on ceruloplasmin was specific to cobalt-protoporphyrin, since eq uimolar doses (25 mu mol/kg body weight) of both tin-protoporphyrin an d iron-protoporphyrin did not produce changes in the levels of circula ting ceruloplasmin. Both inorganic cobalt and cobalt-protoporphyrin pr oduced an elevation in liver cytosolic zinc levels at 48 h. This zinc associated with a fraction that coelutes with authentic metallothionei n standard. These differential effects of inorganic cobalt and cobalt- protoporphyrin on copper and zinc metabolism represent newly defined b iological properties of this trace element and point to the importance of chemical speciation as an underlying factor in the ultimate biolog ical actions of metals.