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

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.

• Keywords
• acute radiation syndrome, hematopoiesis, radiomitigators, radioprotectors,
• MeSH
• Acute Radiation Syndrome drug therapy   prevention & control   MeSH
• Cytokines metabolism   MeSH
• Hematopoietic System drug effects   metabolism   MeSH
• Humans MeSH
• Radiation-Protective Agents therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Cytokines MeSH
• Radiation-Protective Agents 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.

• Keywords
• acute radiation syndrome, combined treatment, cytokines, radiomitigators, radioprotectors,
• MeSH
• Acute Radiation Syndrome drug therapy   metabolism   physiopathology   prevention & control   MeSH
• Amifostine therapeutic use   MeSH
• Dinoprostone therapeutic use   MeSH
• Radiation Injuries, Experimental drug therapy   metabolism   physiopathology   MeSH
• Granulocyte Colony-Stimulating Factor therapeutic use   MeSH
• Drug Combinations MeSH
• Humans MeSH
• Metformin therapeutic use   MeSH
• Misoprostol therapeutic use   MeSH
• Radiation-Protective Agents therapeutic use   MeSH
• Drug Administration Schedule MeSH
• Drug Synergism MeSH
• Vitamin E therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Amifostine MeSH
• Dinoprostone MeSH
• Granulocyte Colony-Stimulating Factor MeSH
• Drug Combinations MeSH
• Metformin MeSH
• Misoprostol MeSH
• Radiation-Protective Agents 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
• Adenosine analogs & derivatives   pharmacology   MeSH
• Adenosine A3 Receptor Agonists pharmacology   MeSH
• Time Factors MeSH
• Whole-Body Irradiation adverse effects   MeSH
• Cyclooxygenase 2 metabolism   MeSH
• Cyclooxygenase 2 Inhibitors pharmacology   MeSH
• Drug Interactions MeSH
• Meloxicam MeSH
• Survival Rate MeSH
• Mice MeSH
• Radiation-Protective Agents pharmacology   MeSH
• Receptor, Adenosine A3 metabolism   MeSH
• Thiazines pharmacology   MeSH
• Thiazoles pharmacology   MeSH
• Gamma Rays adverse effects   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adenosine MeSH
• Adenosine A3 Receptor Agonists MeSH
• Cyclooxygenase 2 MeSH
• Cyclooxygenase 2 Inhibitors MeSH
• Meloxicam MeSH
• N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine MeSH Browser
• Radiation-Protective Agents MeSH
• Receptor, Adenosine A3 MeSH
• Thiazines MeSH
• Thiazoles MeSH