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Inhibition of cyclooxygenase-2 promotes the stimulatory action of adenosine A₃ receptor agonist on hematopoiesis in sublethally γ-irradiated mice
M. Hofer, M. Pospíšil, L. Dušek, Z. Hoferová, L. Weiterová
Language English Country France
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Adenosine administration & dosage analogs & derivatives therapeutic use MeSH
- Adenosine A3 Receptor Agonists administration & dosage therapeutic use MeSH
- Whole-Body Irradiation MeSH
- Erythroid Precursor Cells drug effects radiation effects MeSH
- Radiation Injuries, Experimental blood drug therapy pathology MeSH
- Granulocyte Colony-Stimulating Factor blood MeSH
- Hematinics administration & dosage therapeutic use MeSH
- Hematopoietic Stem Cells drug effects radiation effects MeSH
- Hematopoiesis drug effects radiation effects MeSH
- Cyclooxygenase 2 Inhibitors administration & dosage therapeutic use MeSH
- Drug Therapy, Combination MeSH
- Crosses, Genetic MeSH
- Mice, Inbred CBA MeSH
- Mice MeSH
- Cell Count MeSH
- Granulocyte Precursor Cells drug effects radiation effects MeSH
- Thiazines administration & dosage therapeutic use MeSH
- Thiazoles administration & dosage therapeutic use MeSH
- Gamma Rays adverse effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
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