Radioprotective effects of combination broncho-vaxom, a macrophage activator, and indomethacin, an inhibitor of prostaglandin production: relationship to myelopoiesis.
The effects of the bacterial extract broncho-vaxom (BV; radioprotective immunomodulator; 500 micrograms/mouse i.p., -24 h) and indomethacin (INDO; inhibitor of prostaglandin production; 2 x 40 micrograms/mouse i.m., -24 h and -3 h) on the post-irradiation recovery of hemopoietic functions in mice were investigated. Both agents were administered either alone or in combination. Endogenous spleen colony formation was increased in all treatment groups, with combination-treated mice exhibiting the greatest effects. Similarly, 24 h after combined administration of BV and INDO (i.e. at the time of presumed irradiation) to the non-irradiated mice granulocyte-macrophage colony-forming cell (GM-CFC) numbers were greater in the bone marrow and spleen. Also, as determined by hydroxyurea injection, there was an increase in the number of GM-CFC in the S-phase of the cell cycle in the bone marrow. However, GM-CFC in the spleen of combination pretreated mice was not stimulated to significant proliferation as compared to GM-CFC in the spleen of mice injected with BV alone. Combined modality treatment was also more effective than single agent treatments in accelerating bone marrow cellularity and GM-CFC regeneration, but not in accelerating GM-CFC regeneration in the spleen. Combined administration of BV and INDO to mice prior to lethal irradiation exerted an additional radioprotective effect and protected 95% of the C57Bl/6 mice.
Fedorocko
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P
Department of Cellular and Molecular Biology, Faculty of Sciences, P.H. Safárik University, Kosice, Slovakia.
Macková
O
O
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001419:Bacteria; D001853:Bone Marrow / Q000528:radiation effects; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002457:Cell Extracts; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D003114:Colony-Forming Units Assay; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D006918:Hydroxyurea / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D007700:Kinetics; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D016196:S Phase; D013154:Spleen / Q000166:cytology / Q000528:radiation effects; D013997:Time Factors; D000095983:Bacterial Lysates
D000276:Adjuvants, Immunologic; D002457:Cell Extracts; D016861:Cyclooxygenase Inhibitors; D006918:Hydroxyurea; D007213:Indomethacin; D011837:Radiation-Protective Agents; C030259:Broncho-Vaxom; D000095983:Bacterial Lysates