Previous studies demonstrated that genistein protects mice from radiation-induced bone marrow failure. To overcome genistein's extremely low water solubility, a nanoparticle suspension of genistein has been formulated for more rapid dissolution. In the current study, we evaluated the radioprotective effects of a nanoparticle formulation of genistein on survival and hematopoietic recovery in mice exposed to total-body gamma irradiation. A single intramuscular injection of a saline-based genistein nanosuspension (150 mg/kg) administered to CD2F1 mice 24 h before 9.25 Gy 60Co radiation exposure resulted in a 30-day survival rate of 95% compared to 25% in vehicle-treated animals. In mice irradiated at 7 Gy, the genistein nanosuspension increased mouse bone marrow cellularity from approximately 2.9% (vehicle treated) to 28.3% on day 7 postirradiation. Flow cytometry analysis demonstrated decreased radiation-induced hematopoietic stem and progenitor cell (HSPC, Lineage–/cKit+) death from 77.0% (vehicle) to 43.9% (genistein nanosuspension) with a significant recovery of clonogenicity 7 days after irradiation. The genistein nanosuspension also attenuated the radiation-induced elevation of proinflammatory factors interleukin 1 beta (IL-1β), IL-6 and cyclooxygenase-2 (COX-2) in mouse bone marrow and spleen, which may contribute to protecting HSPCs.
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1 September 2013
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August 14 2013
Genistein Nanoparticles Protect Mouse Hematopoietic System and Prevent Proinflammatory Factors after Gamma Irradiation
Cam T. Ha;
Cam T. Ha
Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889
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Xiang-Hong Li;
Xiang-Hong Li
Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889
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Dadin Fu;
Dadin Fu
Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889
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Mang Xiao;
Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889
2 Address for correspondence: Scientific Research Department, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Ave., Bethesda, MD 20889-5603; e-mail: mang.xiao@usuhs.edu.
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Michael R. Landauer
Michael R. Landauer
1
Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889
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Radiat Res (2013) 180 (3): 316–325.
Article history
Received:
January 30 2013
Accepted:
April 23 2013
Citation
Cam T. Ha, Xiang-Hong Li, Dadin Fu, Mang Xiao, Michael R. Landauer; Genistein Nanoparticles Protect Mouse Hematopoietic System and Prevent Proinflammatory Factors after Gamma Irradiation. Radiat Res 1 September 2013; 180 (3): 316–325. doi: https://doi.org/10.1667/RR3326.1
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