title: 5-androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with radiation-induced myelosuppression.
abstract: Total body ionizing irradiation (TBI) between 2-8 Gy causes the hematopoietic component of the acute radiation syndrome (ARS) in humans. Here we report on an exploratory study with 5-androstenediol (AED) in rhesus monkeys exposed to 4 Gy (60)Co gamma TBI. In this study, the effects of two formulations administered 3-4 h after irradiation were evaluated. After radiation, severe neutropenia (<500 neutrophils/microL), thrombocytopenia (<50,000 platelets/microL), and anemia (hemoglobin <8.0 g/dL) occurred in 6, 6, and 5 of the 6 control animals, respectively. In these 6 control animals, the median time to first day of each defined cytopenia was 8.5, 13, and 20 days and the median time to last occurrence was 22.5, 19.5 and 29.5 days, respectively. All treated groups had a decrease in the duration of severe neutropenia relative to vehicle control. All but one dosing regimen decreased the duration of thrombocytopenia and anemia. Five consecutive days of a 15 mg/kg intramuscular (IM) micro-particle preparation and a once weekly 15 mg/kg subcutaneous (SC) nanoparticle suspension generally provided the greatest radiation protection. AED, as a single agent, promotes multilineage hematopoietic recovery of the bone marrow. These data suggest that it may play an important therapeutic role in the management of acute radiation syndrome.
authors.affiliation: Hollis-Eden Pharmaceuticals, Inc., 4435 Eastgate Mall, Suite 400, San Diego, CA 92121, USA. dstickney@holliseden.com <dstickney@holliseden.com>
authors.forename: Dwight R
authors.initials: DR
authors.lastname: Stickney
authors.forename: Charles
authors.initials: C
authors.lastname: Dowding
authors.forename: Armando
authors.initials: A
authors.lastname: Garsd
authors.forename: Clarence
authors.initials: C
authors.lastname: Ahlem
authors.forename: Mark
authors.initials: M
authors.lastname: Whitnall
authors.forename: Marie
authors.initials: M
authors.lastname: McKeon
authors.forename: Christopher
authors.initials: C
authors.lastname: Reading
authors.forename: James
authors.initials: J
authors.lastname: Frincke
mesh_terms: D015114:Androstenediol / Q000494:pharmacology*; D000740:Anemia / Q000188:drug therapy; D000818:Animals; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D009503:Neutropenia / Q000188:drug therapy; D010316:Particle Size; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000188:drug therapy; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D015114:Androstenediol