Speaker
Dr
Michal Hofer
(Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic)
Description
IB-MECA, an adenosine receptor agonist selective for adenosine A3 receptors, was tested from the point of view of its abilities to influence hematopoiesis in sublethally gamma-irradiated mice and survival of lethally irradiated ones. The drug was administered in therapeutic (post-irradiation) treatment regimens. After a sublethal radiation dose of 4 Gy, IB-MECA was found to stimulate significantly important hematopoietic parameters of the bone marrow progenitor and precursor cells when given i.p. in two doses on days 1 and 2 after irradiation. These hematopoiesis-stimulating effects of IB-MECA manifested itself when the agonist was administered alone. as well as when given concommitantly with granulocyte colony-stimulating factor or an inhibitor of cyclooxygenase-2, meloxicam.
However, following an exposure to lethal doses of gamma-rays, no modulation of survival of the experimental mice by IB-MECA was recoreded, even when various treatment regimens comprising both intraperitoneal and peroral administration routes were attempted.
It follows from the findings that IB-MECA acts as a stimulator of hematopoiesis and, as such, it is maximally effective when administered after sublethal doses of radiation inducing the bone marrow radiation syndrome. After lethal radiation doses, seriously suppressing hematopoiesis and damaging significantly also other organismal systems, like the gastrointestinal one, IB-MECA is, consequently, not efficacious. Since, nevertheless, there are no signs of undesirable side effects of the treatment with IB-MECA in irradiated mice, activation of adenosine A3 receptors may be considered as a usable component in the spetrum of pharmacoloical means potentially utilizable in the treatment of the acute radiation disease.
The work was supported by the Ministry of Defence of the Czech Republic (project Receptor, grant no. 1001 8 5090) and by the Grant Agency of the Czech Republic (grant numbers 305/08/0158 and P303/11/0128).
Author
Dr
Michal Hofer
(Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic)
Co-authors
Dr
Denisa Komůrková
(Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic)
Dr
Lenka Weiterová
(Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic)
Prof.
Milan Pospíšil
(Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic)
Dr
Zuzana Hoferová
(Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic)
