Cobalt protoporphyrin IX induces transient, dose- and time-dependent granulocyte mobilization with mild metabolic effects in mice.

Background: Recombinant granulocyte colony-stimulating factor (G-CSF) is the most commonly used agent for treating neutropenia and mobilizing hematopoietic stem cells (HSCs) for transplantation. However, some patients do not respond effectively to the currently used mobilization protocols. To address this, new therapeutic approaches are needed. A potential strategy is pharmacological induction of endogenous mobilizing factors via cobalt protoporphyrin IX (CoPP). CoPP mobilizes HSCs and granulocytes by increasing endogenous G-CSF, though optimal dosing and potential side effects remain unclear. Our study aimed to optimize CoPP dosing and timing, and assess its safety in mobilizing cells from bone marrow to blood.

Methods: Mice were treated with different doses of CoPP, and blood cell counts, cytokine concentrations, and organ damage markers were evaluated at various time points after injection.

Results: Our results show that CoPP exerts a dose-dependent mobilizing effect, with the highest G-CSF levels and number of mobilized leukocytes observed in mice treated with 10 mg/kg of CoPP. While there were no severe adverse effects, there were mild fluctuations in markers of organ function, including a reduction in blood urea nitrogen (BUN) and glucose levels during the five days of administration. Additionally, although most parameters normalized within 30 days, the decrease in BUN persisted. Mice experienced short-term weight loss following CoPP administration, but they regained their initial weight within two weeks.

Conclusions: This study demonstrates that CoPP mobilizes cells from the bone marrow to the blood in a dose-dependent manner, with mild side effects, including temporary changes in biochemical markers and a sustained reduction in BUN levels.