The Comparative Abilities of Inorganic Cobalt and Cobalt-Protoporphyrin to Affect Copper Metabolism and Elevate Plasma Ceruloplasmin

Abstract

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 µmol/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 µmol/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 µmol/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.

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

“…Systemic CoPPIX administration results in significant toxic side effects (Smith et al 1987;Galbraith and Kappas 1989;Muhoberac et al 1989;Rosenberg and Kappas 1995); however, local administration of CoPPIX to the ear should be examined to determine if HO-1 induction can reduce cisplatin-induced hearing loss. Local administration of CoPPIX (or another HO-1 inducer) would reduce the potential for HO-1 to inhibit the therapeutic efficacy of cisplatin.…”

Cobalt protoporphyrin as a potential therapeutic agent?

“…As already noted by Shan et al , CoPP administration can lead to a depletion of hepatic cytochrome P450 levels and induce weight loss in animals (3, 4). Furthermore, CoPP suppresses thyroid and testicular hormone concentrations in serum, affects copper metabolism, elevates plasma ceruloplasmin levels, and has many other side effects (5, 6). In addition, our own unpublished results reveal that a single injection of 5 mg/kg CoPP, which is the most established experimental dose for in vivo experiments conferring protection in a multitude of experimental models, could have at least transient toxic effects on hepatocellular integrity as shown by increased GPT and LDH serum levels 24 hours after treatment in rats.…”