title: Genistein nanoparticles protect mouse hematopoietic system and prevent proinflammatory factors after gamma irradiation.
abstract: 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 (60)Co 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.
authors: Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889.
authors: Cam T
authors: CT
authors: Ha
authors: Xiang-Hong
authors: XH
authors: Li
authors: Dadin
authors: D
authors: Fu
authors: Mang
authors: M
authors: Xiao
authors: Michael R
authors: MR
authors: Landauer
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D005720:Gamma Rays; D019833:Genistein / Q000008:administration & dosage*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles; D013154:Spleen / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D014916:Whole-Body Irradiation
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D019833:Genistein