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.

• Keywords
• acute radiation syndrome, cyclooxygenase, gastrointestinal system, hematopoiesis, inhibitors of prostaglandin synthesis, prostaglandins,
• MeSH
• Acute Radiation Syndrome blood   drug therapy   etiology   metabolism   MeSH
• Cyclooxygenase 1 metabolism   MeSH
• Cyclooxygenase 2 metabolism   MeSH
• Hematopoiesis drug effects   MeSH
• Cyclooxygenase 2 Inhibitors pharmacology   therapeutic use   MeSH
• Humans MeSH
• Metabolic Networks and Pathways drug effects   MeSH
• Disease Models, Animal MeSH
• Prostaglandins biosynthesis   pharmacology   MeSH
• Radiation-Protective Agents pharmacology   therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Cyclooxygenase 1 MeSH
• Cyclooxygenase 2 MeSH
• Cyclooxygenase 2 Inhibitors MeSH
• Prostaglandins MeSH
• Radiation-Protective Agents 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
• Anti-Inflammatory Agents, Non-Steroidal therapeutic use   MeSH
• Cyclooxygenase 2 metabolism   MeSH
• Dinoprostone metabolism   MeSH
• Granulocyte Colony-Stimulating Factor biosynthesis   blood   MeSH
• Hematopoiesis drug effects   radiation effects   MeSH
• Cyclooxygenase 2 Inhibitors therapeutic use   MeSH
• Humans MeSH
• Meloxicam MeSH
• Myelopoiesis drug effects   radiation effects   MeSH
• Mice MeSH
• Thiazines therapeutic use   MeSH
• Thiazoles therapeutic use   MeSH
• Gamma Rays MeSH
• Feedback, Physiological drug effects   radiation effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Anti-Inflammatory Agents, Non-Steroidal MeSH
• Cyclooxygenase 2 MeSH
• Dinoprostone MeSH
• Granulocyte Colony-Stimulating Factor MeSH
• Cyclooxygenase 2 Inhibitors MeSH
• Meloxicam MeSH
• Thiazines MeSH
• Thiazoles MeSH