Lysosomal Enzyme Release: A Possible Mechanism of Action of Cobalt as an Erythropoietic Stimulant

Abstract

SummaryCobalt produced a significant increase in renal erythropoietic factor activity in the kidney and plasma levels of erythropoietin, which reached peak activity 12 hr after treatment. The studies reported here indicate also that cobalt caused the release of lysosomal enzymes into the blood in vivo. Furthermore, animals treated with cobalt showed increased plasma titers of lysosomal marker enzymes (β-glucuroni-dase and acid phosphatase) at a time when REF activity and plasma ESF levels were approaching a maximum. Metallic ions similar in structure to cobalt (iron, manganese, nickel) did not affect the integrity of lysosomal membranes in vivo. In addition, neither cobalt nor any of the metals tested altered lysosome membrane integrity in vitro.