Most cited article - PubMed ID 24263216
Agonist of the adenosine A3 receptor, IB-MECA, and inhibitor of cyclooxygenase-2, meloxicam, given alone or in a combination early after total body irradiation enhance survival of γ-irradiated mice
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
We investigated and evaluated post-irradiation survival in cyclooxygenase-2-deficient (COX-2 KO) mice. Thirty-day survival following exposure of COX-2 KO mice to a lethal dose of 8.5 Gy of gamma-rays was observed to be statistically significantly lower in both males and females, as well as when the sexes were merged, in comparisons with their wild-type counterparts. These findings were related to the previous observations concerning the detrimental influence of the COX-2 genetic disruption on hematopoiesis in sublethally irradiated mice. Deteriorated post-irradiation survival of COX-2 KO mice confirmed the previously anticipated conclusion regarding negative influence of the antiinflammatory action of COX-2 deficiency under the conditions of exposure of the animals to ionizing radiation.
- MeSH
- Cyclooxygenase 2 deficiency radiation effects MeSH
- Survival Rate trends MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Gamma Rays adverse effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cyclooxygenase 2 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