title: Inhibition of cyclooxygenase-2 promotes the stimulatory action of adenosine A₃ receptor agonist on hematopoiesis in sublethally γ-irradiated mice.
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 1hour after irradiation, IB-MECA in two doses 24 and 48hours 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.
authors: Research Group of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic, Brno, Czech Republic. hofer@ibp.cz
authors: Michal
authors: M
authors: Hofer
authors: Milan
authors: M
authors: Pospíšil
authors: Ladislav
authors: L
authors: Dušek
authors: Zuzana
authors: Z
authors: Hoferová
authors: Lenka
authors: L
authors: Weiterová
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D058909:Adenosine A3 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002452:Cell Count; D003433:Crosses, Genetic; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D042381:Granulocyte Precursor Cells / Q000187:drug effects / Q000528:radiation effects; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D000077239:Meloxicam; D051379:Mice; D008808:Mice, Inbred CBA; D011833:Radiation Injuries, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D013843:Thiazines / Q000008:administration & dosage / Q000627:therapeutic use; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use; D014916:Whole-Body Irradiation
chemical_list: D058909:Adenosine A3 Receptor Agonists; D052246:Cyclooxygenase 2 Inhibitors; D006397:Hematinics; D013843:Thiazines; D013844:Thiazoles; D016179:Granulocyte Colony-Stimulating Factor; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D000241:Adenosine; D000077239:Meloxicam