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 presented review summarizes experimental data obtained with a mouse model when investigating the relationship between inhibition of prostaglandin production and hematopoiesis. While prostaglandin E2 acts in a negative feedback control of myelopoiesis, inhibition of cyclooxygenases, responsible for its production, shifts the feedback to positive control. Based on these relationships, agents inhibiting cyclo-oxygenases, known as non-steroidal anti-inflammatory drugs (NSAIDs), can activate hematopoiesis and be protective or curative under myelosuppressive states. The effectiveness of therapeutic use of NSAIDs in these situations is expressive especially under the selective inhibition of cyclooxygenase-2 (COX-2), when undesirable side effects of cyclooxygenase-1 inhibition, like gastrointestinal damage, are absent. The effects of the clinically approved selective COX-2 inhibitor, meloxicam, were investigated and demonstrated significant hematopoiesis-stimulating and survival-enhancing actions of this drug in sublethally or lethally γ-irradiated mice. These effects were connected with the ability of meloxicam to increase serum levels of the granulocyte colony-stimulating factor. It can be inferred from these findings that selective COX-2 inhibitors might find their use in the treatment of myelosuppressions of various etiologies.

• MeSH
• antiflogistika nesteroidní terapeutické užití   MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• dinoproston metabolismus   MeSH
• faktor stimulující kolonie granulocytů biosyntéza   krev   MeSH
• hematopoéza účinky léků   účinky záření   MeSH
• inhibitory cyklooxygenasy 2 terapeutické užití   MeSH
• lidé MeSH
• meloxikam MeSH
• myelopoéza účinky léků   účinky záření   MeSH
• myši MeSH
• thiaziny terapeutické užití   MeSH
• thiazoly terapeutické užití   MeSH
• záření gama MeSH
• zpětná vazba fyziologická účinky léků   účinky záření   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• cyklooxygenasa 2 MeSH
• dinoproston MeSH
• faktor stimulující kolonie granulocytů MeSH
• inhibitory cyklooxygenasy 2 MeSH
• meloxikam MeSH
• thiaziny MeSH
• thiazoly MeSH