In recent times, cytokines and hematopoietic growth factors have been at the center of attention for many researchers trying to establish pharmacological therapeutic procedures for the treatment of radiation accident victims. Two granulocyte colony-stimulating factor-based radiation countermeasures have been approved for the treatment of the hematopoietic acute radiation syndrome. However, at the same time, many different substances with varying effects have been tested in animal studies as potential radioprotectors and mitigators of radiation damage. A wide spectrum of these substances has been studied, comprising various immunomodulators, prostaglandins, inhibitors of prostaglandin synthesis, agonists of adenosine cell receptors, herbal extracts, flavonoids, vitamins, and others. These agents are often effective, relatively non-toxic, and cheap. This review summarizes the results of animal experiments, which show the potential for some of these untraditional or new radiation countermeasures to become a part of therapeutic procedures applicable in patients with the acute radiation syndrome. The authors consider β-glucan, 5-AED (5-androstenediol), meloxicam, γ-tocotrienol, genistein, IB-MECA (N⁶-(3-iodobezyl)adenosine-5'-N-methyluronamide), Ex-RAD (4-carboxystyryl-4-chlorobenzylsulfone), and entolimod the most promising agents, with regards to their contingent use in clinical practice.

• Klíčová slova
• acute radiation syndrome, hematopoiesis, radiomitigators, radioprotectors,
• MeSH
• akutní radiační syndrom farmakoterapie   prevence a kontrola   MeSH
• cytokiny metabolismus   MeSH
• hematopoetický systém účinky léků   metabolismus   MeSH
• lidé MeSH
• radioprotektivní látky terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• radioprotektivní látky MeSH

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.

• Klíčová slova
• acute radiation syndrome, combined treatment, cytokines, radiomitigators, radioprotectors,
• MeSH
• akutní radiační syndrom farmakoterapie   metabolismus   patofyziologie   prevence a kontrola   MeSH
• amifostin terapeutické užití   MeSH
• dinoproston terapeutické užití   MeSH
• experimentální radiační poranění farmakoterapie   metabolismus   patofyziologie   MeSH
• faktor stimulující kolonie granulocytů terapeutické užití   MeSH
• fixní kombinace léků MeSH
• lidé MeSH
• metformin terapeutické užití   MeSH
• misoprostol terapeutické užití   MeSH
• radioprotektivní látky terapeutické užití   MeSH
• rozvrh dávkování léků MeSH
• synergismus léků MeSH
• vitamin E terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• amifostin MeSH
• dinoproston MeSH
• faktor stimulující kolonie granulocytů MeSH
• fixní kombinace léků MeSH
• metformin MeSH
• misoprostol MeSH
• radioprotektivní látky MeSH
• vitamin E MeSH

Adenosine A3 receptor knockout (A3AR KO) mice and their wild-type (WT) counterparts were compared from the point of view of their abilities to survive exposures to lethal doses of γ-radiation belonging to the range of radiation doses inducing the bone marrow acute radiation syndrome. Parameters of cumulative 30-day survival (experiment using a midlethal radiation dose) or cumulative 11-day survival (experiment using an absolutely lethal radiation dose), and of mean survival time were evaluated. The values of A3AR KO mice always reflected their higher survival in comparison with WT ones, the P values being above the limit for statistical significance after the midlethal radiation dose and standing for statistical significance after the absolutely lethal radiation dose. This finding was considered surprising, taking into account the previously obtained findings on defects in numbers and functional properties of peripheral blood cells in A3AR KO mice. Therefore, previous hematological analyses of A3AR KO mice were supplemented in the present studies with determination of serum levels of the granulocyte colony-stimulating factor, erythropoietin, and thrombopoietin. Though distinct differences in these parameters were observed between A3AR KO and WT mice, none of them could explain the relatively high postirradiation survival of A3AR KO mice. Further studies on these mice comprising also those on other than hemopoietic tissues and organs can help to clarify their relative radioresistance.

• MeSH
• akutní radiační syndrom genetika   metabolismus   mortalita   MeSH
• míra přežití MeSH
• myši knockoutované MeSH
• myši MeSH
• receptor adenosinový A3 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptor adenosinový A3 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
• hematopoetické kmenové buňky metabolismus   MeSH
• hematopoéza fyziologie   MeSH
• leukocyty mononukleární metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• receptor adenosinový A3 nedostatek   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptor adenosinový 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
• akutní radiační syndrom farmakoterapie   patologie   MeSH
• časové faktory MeSH
• faktor stimulující kolonie granulocytů biosyntéza   terapeutické užití   MeSH
• interleukin-3 terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• kostní dřeň patologie   účinky záření   MeSH
• lidé MeSH
• membránové proteiny terapeutické užití   MeSH
• rekombinantní proteiny terapeutické užití   MeSH
• rozvrh dávkování léků MeSH
• růstový faktor kmenových buněk terapeutické užití   MeSH
• thrombopoetin terapeutické užití   MeSH
• únik radioaktivních látek MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• faktor stimulující kolonie granulocytů MeSH
• flt3 ligand protein MeSH Prohlížeč
• interleukin-3 MeSH
• membránové proteiny MeSH
• rekombinantní proteiny MeSH
• růstový faktor kmenových buněk MeSH
• thrombopoetin MeSH

There exists a requirement for drugs which would be useful in therapy of an acute radiation damage of a mammalian organism. The aim of the study was to evaluate survival parameters in mice exposed to a lethal γ-ray dose of 8.5 Gy and treated with single doses of an adenosine A(3) receptor agonist, IB-MECA, or a cyclooxygenase-2 (COX-2) inhibitor, meloxicam, administered alone or in a combination early after irradiation, i.e., 0.5 and 1 h post-irradiation, respectively. The assessed parameters were the mean survival time (MST) and the cumulative percentage 30-day survival (CPS). Administrations of single intraperitoneal doses of either IB-MECA 0.5 h post-irradiation or meloxicam 1 h post-irradiation resulted in statistically significant increases of MST in comparison with the control irradiated mice. Combined administration of IB-MECA and meloxicam was found to be the only treatment statistically enhancing the parameter of CPS and to lead to the most expressive increase in MST of the experimental mice. The findings add new knowledge on the action of an adenosine A3 receptor agonist and a COX-2 inhibitor in an irradiated mammalian organism and suggest the potential of both the investigated drugs in the treatment of the acute radiation damage.

• MeSH
• adenosin analogy a deriváty   farmakologie   MeSH
• agonisté adenosinového receptoru A3 farmakologie   MeSH
• časové faktory MeSH
• celotělové ozáření škodlivé účinky   MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• inhibitory cyklooxygenasy 2 farmakologie   MeSH
• lékové interakce MeSH
• meloxikam MeSH
• míra přežití MeSH
• myši MeSH
• radioprotektivní látky farmakologie   MeSH
• receptor adenosinový A3 metabolismus   MeSH
• thiaziny farmakologie   MeSH
• thiazoly farmakologie   MeSH
• záření gama škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosin MeSH
• agonisté adenosinového receptoru A3 MeSH
• cyklooxygenasa 2 MeSH
• inhibitory cyklooxygenasy 2 MeSH
• meloxikam MeSH
• N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine MeSH Prohlížeč
• radioprotektivní látky MeSH
• receptor adenosinový A3 MeSH
• thiaziny MeSH
• thiazoly 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
• hematopoéza účinky léků   MeSH
• lidé MeSH
• purinergní receptory P1 účinky léků   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• purinergní receptory P1 MeSH