The goal of combined pharmacological approaches in the treatment of the acute radiation syndrome (ARS) is to obtain an effective therapy producing a minimum of undesirable side effects. This review summarizes important data from studies evaluating the efficacy of combining radioprotective agents developed for administration prior to irradiation and therapeutic agents administered in a post-irradiation treatment regimen. Many of the evaluated results show additivity, or even synergism, of the combined treatments in comparison with the effects of the individual component administrations. It can be deduced from these findings that the research in which combined treatments with radioprotectors/radiomitigators are explored, tested, and evaluated is well-founded. The requirement for studies highly emphasizing the need to minimize undesirable side effects of the radioprotective/radiomitigating therapies is stressed.

• Keywords
• acute radiation syndrome, combined treatment, cytokines, radiomitigators, radioprotectors,
• MeSH
• Acute Radiation Syndrome drug therapy   metabolism   physiopathology   prevention & control   MeSH
• Amifostine therapeutic use   MeSH
• Dinoprostone therapeutic use   MeSH
• Radiation Injuries, Experimental drug therapy   metabolism   physiopathology   MeSH
• Granulocyte Colony-Stimulating Factor therapeutic use   MeSH
• Drug Combinations MeSH
• Humans MeSH
• Metformin therapeutic use   MeSH
• Misoprostol therapeutic use   MeSH
• Radiation-Protective Agents therapeutic use   MeSH
• Drug Administration Schedule MeSH
• Drug Synergism MeSH
• Vitamin E therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Amifostine MeSH
• Dinoprostone MeSH
• Granulocyte Colony-Stimulating Factor MeSH
• Drug Combinations MeSH
• Metformin MeSH
• Misoprostol MeSH
• Radiation-Protective Agents MeSH
• Vitamin E MeSH

This study continues our earlier findings on the hematopoiesis-modulating effects of adenosine A1 and A3 receptor agonists that were performed on committed hematopoietic progenitor and precursor cell populations. In the earlier experiments, N (6)-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, was found to inhibit proliferation in the above-mentioned hematopoietic cell systems, whereas N (6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), an adenosine A3 receptor agonist, was found to stimulate it. The topic of this study was to evaluate the possibility that the above-mentioned adenosine receptor agonists modulate the behavior of early hematopoietic progenitor cells and hematopoietic stem cells. Flow cytometric analysis of hematopoietic stem cells in mice was employed, as well as a functional test of hematopoietic stem and progenitor cells (HSPCs). These techniques enabled us to study the effect of the agonists on both short-term repopulating ability and long-term repopulating ability, representing multipotent progenitors and hematopoietic stem cells, respectively. In a series of studies, we did not find any significant effect of adenosine agonists on HSPCs in terms of their numbers, proliferation, or functional activity. Thus, it can be concluded that CPA and IB-MECA do not significantly influence the primitive hematopoietic stem and progenitor cell pool and that the hematopoiesis-modulating action of these adenosine receptor agonists is restricted to more mature compartments of hematopoietic progenitor and precursor cells.

• MeSH
• Purinergic P1 Receptor Agonists pharmacology   MeSH
• Hematopoietic Stem Cells drug effects   physiology   MeSH
• Hematopoiesis drug effects   physiology   MeSH
• Multipotent Stem Cells drug effects   physiology   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Flow Cytometry MeSH
• Receptor, Adenosine A1 metabolism   MeSH
• Receptor, Adenosine A3 metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Purinergic P1 Receptor Agonists MeSH
• Receptor, Adenosine A1 MeSH
• Receptor, Adenosine A3 MeSH

The review summarizes data evaluating the role of adenosine receptor signaling in murine hematopoietic functions. The studies carried out utilized either non-selective activation of adenosine receptors induced by elevation of extracellular adenosine or by administration of synthetic adenosine analogs having various proportions of selectivity for a particular receptor. Numerous studies have described stimulatory effects of non-selective activation of adenosine receptors, manifested as enhancement of proliferation of cells at various levels of the hematopoietic hierarchy. Subsequent experimental approaches, considering the hematopoiesis-modulating action of adenosine receptor agonists with a high level of selectivity to individual adenosine receptor subtypes, have revealed differential effects of various adenosine analogs. Whereas selective activation of A₁ receptors has resulted in suppression of proliferation of hematopoietic progenitor and precursor cells, that of A₃ receptors has led to stimulated cell proliferation in these cell compartments. Thus, A₁ and A₃ receptors have been found to play a homeostatic role in suppressed and regenerating hematopoiesis. Selective activation of adenosine A₃ receptors has been found to act curatively under conditions of drug- and radiation-induced myelosuppression. The findings in these and further research areas will be summarized and mechanisms of hematopoiesis-modulating action of adenosine receptor agonists will be discussed.

• MeSH
• Hematopoiesis drug effects   MeSH
• Humans MeSH
• Receptors, Purinergic P1 drug effects   MeSH
• Signal Transduction MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Receptors, Purinergic P1 MeSH