5-androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with radiation-induced myelosuppression.
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.
Stickney
Dwight R
DR
Hollis-Eden Pharmaceuticals, Inc., 4435 Eastgate Mall, Suite 400, San Diego, CA 92121, USA. dstickney@holliseden.com <dstickney@holliseden.com>
Dowding
Charles
C
Garsd
Armando
A
Ahlem
Clarence
C
Whitnall
Mark
M
McKeon
Marie
M
Reading
Christopher
C
Frincke
James
J
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*
D015114:Androstenediol