Prostaglandins and inhibitors of their synthesis (cyclooxygenase (COX) inhibitors, non-steroidal anti-inflammatory drugs) were shown to play a significant role in the regulation of hematopoiesis. Partly due to their hematopoiesis-modulating effects, both prostaglandins and COX inhibitors were reported to act positively in radiation-exposed mammalian organisms at various pre- and post-irradiation therapeutical settings. Experimental efforts were targeted at finding pharmacological procedures leading to optimization of therapeutical outcomes by minimizing undesirable side effects of the treatments. Progress in these efforts was obtained after discovery of selective inhibitors of inducible selective cyclooxygenase-2 (COX-2) inhibitors. Recent studies have been able to suggest the possibility to find combined therapeutical approaches utilizing joint administration of prostaglandins and inhibitors of their synthesis at optimized timing and dosing of the drugs which could be incorporated into the therapy of patients with acute radiation syndrome.

• Klíčová slova
• acute radiation syndrome, cyclooxygenase, gastrointestinal system, hematopoiesis, inhibitors of prostaglandin synthesis, prostaglandins,
• MeSH
• akutní radiační syndrom krev   farmakoterapie   etiologie   metabolismus   MeSH
• cyklooxygenasa 1 metabolismus   MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• hematopoéza účinky léků   MeSH
• inhibitory cyklooxygenasy 2 farmakologie   terapeutické užití   MeSH
• lidé MeSH
• metabolické sítě a dráhy účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• prostaglandiny biosyntéza   farmakologie   MeSH
• radioprotektivní látky farmakologie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cyklooxygenasa 1 MeSH
• cyklooxygenasa 2 MeSH
• inhibitory cyklooxygenasy 2 MeSH
• prostaglandiny MeSH
• radioprotektivní látky MeSH

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

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