Inhibition of cyclooxygenase-2 promotes the stimulatory action of adenosine A3 receptor agonist on hematopoiesis in sublethally γ-irradiated mice

• Published in: Biomedicine & pharmacotherapy 2011-09, Vol.65 (6), p.427-431
• Main Authors: Hofer, Michal, Pospíšil, Milan, Dušek, Ladislav, Hoferová, Zuzana, Weiterová, Lenka
• Format: Article
• Language: English
• Subjects: Adenosine - administration & dosage; Adenosine - analogs & derivatives; Adenosine - therapeutic use; Adenosine A3 Receptor Agonists - administration & dosage; Adenosine A3 Receptor Agonists - therapeutic use; Animals; Cell Count; Crosses, Genetic; Cyclooxygenase 2 Inhibitors - administration & dosage; Cyclooxygenase 2 Inhibitors - therapeutic use; Drug Therapy, Combination; Erythroid Precursor Cells - drug effects; Erythroid Precursor Cells - radiation effects; Gamma Rays - adverse effects; Granulocyte Colony-Stimulating Factor - blood; Granulocyte Precursor Cells - drug effects; Granulocyte Precursor Cells - radiation effects; Hematinics - administration & dosage; Hematinics - therapeutic use; Hematopoiesis - drug effects; Hematopoiesis - radiation effects; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - radiation effects; Internal Medicine; Male; Medical Education; Mice; Mice, Inbred CBA; Radiation Injuries, Experimental - blood; Radiation Injuries, Experimental - drug therapy; Radiation Injuries, Experimental - pathology; Thiazines - administration & dosage; Thiazines - therapeutic use; Thiazoles - administration & dosage; Thiazoles - therapeutic use; Whole-Body Irradiation
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2011.04.033

Abstract Mouse hematopoiesis, suppressed by a sublethal dose of ionizing radiation, was the target for combined therapy with a cyclooxygenase-2 (COX-2) inhibitor meloxicam and an adenosine A3 receptor agonist IB-MECA. The drugs were administered in an early postirradiation treatment regimen: meloxicam was given in a single dose 1 hour after irradiation, IB-MECA in two doses 24 and 48 hours after irradiation. Treatment-induced changes in several compartments of hematopoietic progenitor and precursor cells of the bone marrow were evaluated on day 3 after irradiation. Values of hematopoietic progenitor cells for granulocytes/macrophages and erythrocytes (GM-CFC and BFU-E, respectively), as well as those of proliferative granulocytic cells were found to be significantly higher in the mice treated with the drug combination in comparison to irradiated controls and attained the highest increase factors of 1.6, 1.6, and 2.6, respectively. The study emphasizes the significance of the combined treatment of suppressed hematopoiesis with more agents. Mechanisms of the action of the individual compounds of the studied drug combination and of their joint operation are discussed.