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

The role of the adenosine A3 receptor in hematopoiesis was studied using adenosine A3 receptor knockout (A3AR KO) mice. Hematological parameters of peripheral blood and femoral bone marrow of irradiated and untreated A3AR KO mice and their wild-type (WT) counterparts were investigated. Irradiation of the mice served as a defined hematopoiesis-damaging means enabling us to evaluate contingent differences in the pattern of experimentally induced hematopoietic suppression between the A3AR KO mice and WT mice. Defects were observed in the counts and/or functional parameters of blood cells in the A3AR KO mice. These defects include statistically significantly lower values of blood neutrophil and monocyte counts, as well as those of mean erythrocyte volume, mean erythrocyte hemoglobin, blood platelet counts, mean platelet volume, and plateletcrit, and can be considered to bear evidence of the lack of a positive role played by the adenosine A3 receptor in the hematopoietic system. Statistically significantly increased values of the bone marrow parameters studied in A3AR KO mice (femoral bone marrow cellularity, granulocyte/macrophage progenitor cells, and erythrocyte progenitor cells) can probably be explained by compensatory mechanisms attempting to offset the disorders in the function of blood elements in these mice. The pattern of the radiation-induced hematopoietic suppression was very similar in A3AR KO mice and their WT counterparts.

• MeSH
• Hematopoietic Stem Cells metabolism   MeSH
• Hematopoiesis physiology   MeSH
• Leukocytes, Mononuclear metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Receptor, Adenosine A3 deficiency   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
• Receptor, Adenosine A3 MeSH

This article concisely summarizes data on the action of one of the principal and best known growth factors, the granulocyte colony-stimulating factor (G-CSF), in a mammalian organism exposed to radiation doses inducing acute radiation syndrome. Highlighted are the topics of its real or anticipated use in radiation accident victims, the timing of its administration, the possibilities of combining G-CSF with other drugs, the ability of other agents to stimulate endogenous G-CSF production, as well as of the capability of this growth factor to ameliorate not only the bone marrow radiation syndrome but also the gastrointestinal radiation syndrome. G-CSF is one of the pivotal drugs in the treatment of radiation accident victims and its employment in this indication can be expected to remain or even grow in the future.

• MeSH
• Acute Radiation Syndrome drug therapy   pathology   MeSH
• Time Factors MeSH
• Granulocyte Colony-Stimulating Factor biosynthesis   therapeutic use   MeSH
• Interleukin-3 therapeutic use   MeSH
• Drug Therapy, Combination MeSH
• Bone Marrow pathology   radiation effects   MeSH
• Humans MeSH
• Membrane Proteins therapeutic use   MeSH
• Recombinant Proteins therapeutic use   MeSH
• Drug Administration Schedule MeSH
• Stem Cell Factor therapeutic use   MeSH
• Thrombopoietin therapeutic use   MeSH
• Radioactive Hazard Release 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
• Granulocyte Colony-Stimulating Factor MeSH
• flt3 ligand protein MeSH Browser
• Interleukin-3 MeSH
• Membrane Proteins MeSH
• Recombinant Proteins MeSH
• Stem Cell Factor MeSH
• Thrombopoietin 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