title: 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.
abstract: 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.
authors.affiliation: Department of Molecular Cytology and Cytometry, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic, Královopolská 135, 61265, Brno, Czech Republic, hofer@ibp.cz.
authors.forename: Michal
authors.initials: M
authors.lastname: Hofer
authors.forename: Milan
authors.initials: M
authors.lastname: Pospíšil
authors.forename: Ladislav
authors.initials: L
authors.lastname: Dušek
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Hoferová
authors.forename: Denisa
authors.initials: D
authors.lastname: Komůrková
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D005720:Gamma Rays / Q000009:adverse effects*; D008297:Male; D000077239:Meloxicam; D051379:Mice; D011837:Radiation-Protective Agents / Q000494:pharmacology; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D015996:Survival Rate; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D058909:Adenosine A3 Receptor Agonists; D052246:Cyclooxygenase 2 Inhibitors; D011837:Radiation-Protective Agents; D043684:Receptor, Adenosine A3; D013843:Thiazines; D013844:Thiazoles; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D051546:Cyclooxygenase 2; D000241:Adenosine; D000077239:Meloxicam