Liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) promotes haemopoietic recovery in irradiated mouse.
Pretreatment of C57B1/6 mouse with the macrophage activator muramyl tripeptide phosphatidylethanolamine encapsulated in liposomes (MTP-PE/MLV) induced haemopoietic recovery in subsequently irradiated mouse. An optimal endoCFU-S survival was observed when 200 micrograms MTP-PE/MLV was administered i.p. 24 h before irradiation. MTP-PE/MLV did not affect the day 8 exogenous CFU-S survival in the bone marrow immediately after irradiation. However, 3, 6, 9 and 14 days after irradiation the number of day 8 CFU-S was almost 2 to 4-fold higher in the bone marrow of the MTP-PE/MLV injected mouse. Also, recovery of the GM-CFC pools in femoral bone marrow after irradiation proceeded at a faster rate in the MTP-PE/MLV-treated animal than in control groups. After a single i.p. injection of MTP-PE/MLV to the non-irradiated mouse, the number of CFU-S in bone marrow was not significantly different from controls, whereas the number of GM-CSC was significantly increased. In addition, the percentage of day 8 CFU-S and GM-CFC in S-phase of the cell cycle was significantly increased, as was colony-stimulating activity present in the serum of treated animals. Pretreatment with MTP-PE/MLV protected the C57Bl/6 mouse in a dose-dependent manner from the lethal effects of ionizing radiation. A single dose (100 or 200 micrograms) injected i.p. 24 h, or 100 micrograms MTP-PE/MLV injected i.v. 24 h before 9.5 Gy gamma-rays protected 47, 85 and 59% of C57B1/6 mouse, respectively. The dose reduction factor in the case when the MTP-PE/MLV (200 micrograms per mouse) was administered i.p. at that time was 1.17 (95% CL 1.13, 1.21). Combined administration of MTP-PE/MLV (24 h) and indomethacin (24 and 3 h) to mouse prior to irradiation exerted an additional radioprotective effect.
Fedorocko
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Department of Cellular and Molecular Biology, Faculty of Sciences, P. J. Safárik University, Kosice, Slovak Republic.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells; D004337:Drug Carriers; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000528:radiation effects; D006402:Hematologic Diseases / Q000209:etiology / Q000517:prevention & control*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects*; D008081:Liposomes; D008264:Macrophages / Q000166:cytology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010714:Phosphatidylethanolamines / Q000008:administration & dosage* / Q000627:therapeutic use; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D014916:Whole-Body Irradiation
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine