Oral oxymetholone reduces mortality induced by gamma irradiation in mice through stimulation of hematopoietic cells

Mol Cell Biochem. 2006 Jul;287(1-2):193-9. doi: 10.1007/s11010-005-9111-5. Epub 2006 Mar 11.

Abstract

Oxymetholone is a 17alpha -alkylated anabolic-androgenic steroid. This drug can stimulate bone marrow cells and increase the blood cells in the peripheral blood vessels. It has been used for the treatment of anemia caused by low red cell production. Since oxymetholone has hematopoietic effect, we studied radioprotective effects of this drug in mice. In this study, we determined percentage of survival, dose-reduction factor (DRF) and hematological parameters in irradiated mice which treated with or without oxymetholone. Oxymetholone administrated at different doses 80, 160, 320, 640 mg/kg by gavages at 24 h before 8 Gy gamma irradiation. At 30 days after treatment, the following percentage of animals survival in each group was as: 80 mg/kg, 50%; 160 mg/kg, 50%; 320 mg/kg, 55%; 640 mg/kg, 75% and vehicle, 15%. Percentage of survival increased in all of treated groups statistically compared with irradiated-vehicle group. In the groups treated by oxymetholone, maximum protection was realized at 640 mg/kg. In order to calculate the DRF for oxymetholone, mice were exposed to whole-body gamma irradiation with dose ranges between 5.83 and 11.23 Gy. The probit line for oxymetholone-treated mice was shifted to the right with a DRF of 1.14. In mice exposed to whole-body gamma-irradiation (4 Gy), an oral administration of 640 mg/kg oxymetholone ameliorated radiation-induced decreases in circulating platelets and erythrocytes, but had a less effect on total number of WBC. These results demonstrate that oxymetholone stimulates myelopoiesis and thrombocytopenia and enhances survival in mice after ionizing radiation.

MeSH terms

  • Animals
  • Blood Cells / drug effects
  • Blood Cells / radiation effects
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Evaluation, Preclinical
  • Gamma Rays*
  • Hematopoietic System / cytology
  • Hematopoietic System / drug effects*
  • Mice
  • Myelopoiesis / drug effects
  • Oxymetholone / administration & dosage
  • Oxymetholone / therapeutic use*
  • Radiation Injuries / drug therapy*
  • Radiation Injuries / mortality*
  • Radiation-Protective Agents / administration & dosage
  • Radiation-Protective Agents / therapeutic use*
  • Survival Rate
  • Thrombocytopenia / chemically induced

Substances

  • Radiation-Protective Agents
  • Oxymetholone