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.
- 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
Gastrointestinal form is the second stage of acute radiation syndrome (ARS) with a threshold dose of 8 Gy in man. It represents an absolutely lethal clinical-pathological unit, necrohemorrhagic enteritis and proctocolitis, with unknown causal therapy. Elk-1 is a protein acting as a transcription factor activating specified genes. The purpose of our study was to examine the expression of phospho-Elk-1 in irradiated jejunum and transversal colon of rats with radiation-induced enterocolitis and to assess the importance of this transcriptional factor as a biodosimetric marker of radiation-induced enteropathy. The laboratory rats were randomly divided into 21 groups, 10 animals per group, and irradiated with whole body ?-irradiation of 1, 5, 10, 15, and 20 Gy. Samples of jejunum and transversal colon were taken 24, 48, 72, and 96 hours later, immunohistochemically stained, and the phospho-Elk-1 expression was examined using computer image analysis. A group of 10 shamirradiated animals was used as control. Significantly increased expression of phospho-Elk-1 in rat jejunum has been found in all time intervals after irradiation by sublethal doses of 1 and 5 Gy, whereas after the irradiation by lethal doses, the expression of phospho-Elk-1 in rat jejunum varied considerably. Significantly increased expression of phospho-Elk-1 in transversal colon has also been found in the first days after irradiation by sublethal doses of 1 and 5 Gy. After irradiation by lethal doses, tere was no uniform pattern of the changes in the expression of phospho-Elk- 1 in rat transversal colon. The detection of phospho-Elk-1 might be considered as a suitable and very sensitive biodosimetric marker of radiation-induced injury of small and large intestine. According to our knowledge, this is the first study on the phospho-Elk-1 expression in irradiated jejunum and transversal colon in the rat.
- Klíčová slova
- Radiation-induced entero-colitis, Phospho-Elk-1 expression, Biodosimetric marker,
- MeSH
- akutní radiační syndrom etiologie metabolismus MeSH
- biologické markery metabolismus MeSH
- časové faktory MeSH
- celotělové ozáření MeSH
- enterokolitida etiologie metabolismus MeSH
- experimentální radiační poranění etiologie metabolismus MeSH
- fosforylace MeSH
- jejunum metabolismus účinky záření MeSH
- kolon metabolismus účinky záření MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- protein Elk-1 s doménou ets metabolismus MeSH
- upregulace MeSH
- vztah dávky záření a odpovědi MeSH
- záření gama MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH