5-androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression

Int Immunopharmacol. 2007 Apr;7(4):500-5. doi: 10.1016/j.intimp.2006.12.005. Epub 2007 Jan 12.

Abstract

We previously reported that five daily intramuscular doses of 5-androstenediol (AED), a naturally occurring adrenal steroid hormone, stimulated multilineage recovery of bone marrow in rhesus monkeys with radiation-induced myelosuppression after 4.0 Gy total body irradiation (TBI). Here we report the effect of AED on the survival of eighty rhesus macaques that received a 6.0 Gy dose of TBI in four sequential pilot studies. The drug was administered intramuscularly, based on body weight, 2-4 h after irradiation and continued once daily for a total of five injections. No clinical support in the form of antibiotics or transfusions was given to the animals at any time during the study. Five of the 40 (12.5%) treated animals died, compared to 13 of 40 (32.5%) of the animals in the control group (p=0.032). The combination of accumulated days of thrombocytopenia (<20,000 platelets/microL) up to day 14 (before the first death) together with treatment, accurately predicts mortality (p<0.001). The compound significantly reduced the duration of thrombocytopenia and neutropenia (p<0.01). The accumulation of days of neutropenia (ANC<500 cells/microL) up to day 14 plays no major role in predicting death. AED shows significant activity in irradiated primates with acute hematopoietic radiation syndrome.

MeSH terms

  • Androstenediol / pharmacology*
  • Animals
  • Female
  • Gamma Rays*
  • Macaca mulatta
  • Male
  • Radiation Injuries, Experimental / drug therapy*
  • Radiation Injuries, Experimental / mortality
  • Radiation-Protective Agents / pharmacology*
  • Thrombocytopenia / drug therapy
  • Thrombocytopenia / mortality
  • X-Rays*

Substances

  • Radiation-Protective Agents
  • Androstenediol