Drugs elevating extracellular adenosine promote regeneration of haematopoietic progenitor cells in severely myelosuppressed mice: their comparison and joint effects with the granulocyte colony-stimulating factor
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
- MeSH
- adenosin metabolismus MeSH
- adenosinmonofosfát farmakologie terapeutické užití MeSH
- celotělové ozáření škodlivé účinky MeSH
- dipyridamol farmakologie terapeutické užití MeSH
- erytroidní prekurzorové buňky patologie MeSH
- extracelulární prostor metabolismus MeSH
- faktor stimulující kolonie granulocytů farmakologie terapeutické užití MeSH
- hematopoetické kmenové buňky patologie MeSH
- karboplatina toxicita MeSH
- kostní dřeň účinky léků patologie účinky záření MeSH
- krevní obraz MeSH
- lymfocyty patologie MeSH
- makrofágy patologie MeSH
- myši inbrední C57BL MeSH
- myši inbrední CBA MeSH
- myši MeSH
- pancytopenie farmakoterapie etiologie metabolismus patologie MeSH
- preklinické hodnocení léčiv MeSH
- prekurzory léčiv farmakologie terapeutické užití MeSH
- synergismus léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- adenosin MeSH
- adenosinmonofosfát MeSH
- dipyridamol MeSH
- faktor stimulující kolonie granulocytů MeSH
- karboplatina MeSH
- prekurzory léčiv MeSH
We tested capabilities of drugs elevating extracellular adenosine and of granulocyte colony-stimulating factor (G-CSF) given alone or in combination to modulate regeneration from severe myelosuppression resulting from combined exposure of mice to ionizing radiation and carboplatin. Elevation of extracellular adenosine was induced by joint administration of dipyridamole (DP), a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), serving as an adenosine prodrug. DP+AMP, G-CSF or all these drugs in combination were administered in a 4-d treatment regimen starting on day 3 after induction of myelosuppression. Comparable enhancements of haematopoietic regeneration due to elevation of extracellular adenosine or to action of G-CSF were demonstrated as shown by elevated numbers of haematopoietic progenitor cells for granulocytes/macrophages (GM-CFC) and erythrocytes (BFU-E) in the bone marrow and spleen in early time intervals after termination of the drug treatment, i.e. on days 7 and 10 after induction of myelosuppression. Coadministration of all the drugs further potentiated the restoration of progenitor cell pools in the haematopoietic organs. The effects of the drug treatments on progenitor cells were reflected in the peripheral blood in later time intervals of days 15 and 20 after induction of myelosuppression, especially as significantly elevated numbers of granulocytes and less pronounced elevation of lymphocytes and erythrocytes. The results substantiate the potential of drugs elevating extracellular adenosine for clinical utilization in myelosuppressive states, e.g. those accompanying oncological radio- and chemotherapy.
Citace poskytuje Crossref.org
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The role of adenosine receptor agonists in regulation of hematopoiesis
