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Molecular and Cellular Biochemistry

, Volume 287, Issue 1–2, pp 193–199 | Cite as

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

  • Seyed Jalal HosseinimehrEmail author
  • Valiallah Zakaryaee
  • Mohsen Froughizadeh
Article

Abstract

Oxymetholone is a 17α -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.

Keywords

radioprotective oxymetholone hematopoietic survival radiation 

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References

  1. 1.
    Whitnall MH, Elliott TB, Harding RA, Inal CE, Landauer MR, Wilhelmsen CL, MacKinney L, Miner VL, Jackson WE, Loria RM, Ledney GD, Seed TM: Androstendiol stimulates myelopoiesis and enhances resistance to infectionin gamma-irradiated mice. Inter J Immunopharm 22: 1–14, 2000CrossRefGoogle Scholar
  2. 2.
    Nunia V, Goyal PK: Prevention of gamma radiation induced anemia in miceby diltiazem. J Radiat Res 45: 11–17, 2004PubMedCrossRefGoogle Scholar
  3. 3.
    Drouet M, Mourcin F, Grenier N, Leroux V, Denis J, Mayol JF, Thullier P, Lataillade JJ, Herodin F: Single administration of stem cell factor, FLT-3 ligand, megakaryocyte growth and development factor, and interleukin-3 in combination soon after irradiation prevents nonhuman primates frommyelosuppresion: long-term follow-up. Blood 103: 878–885, 2004PubMedCrossRefGoogle Scholar
  4. 4.
    Farese AM, Hunt P, Grab LB, MacVittie TJ: Combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor enhances multilineage hematopoietic reconstitution in nonhuman primates after radiation-induced marrow aplasia.J Clin Invest 97: 2145–2151, 1996PubMedCrossRefGoogle Scholar
  5. 5.
    Hosseinimehr SJ, Shafiee A, Mozdarani H, Akhlagpour S: Radioprotective effects of 2-iminothiazolidine derivatives against lethal dose of gammaradiation in mice. J Radiat Res 42: 401–408, 2001PubMedCrossRefGoogle Scholar
  6. 6.
    Hosseinimehr SJ, Shafiee A, Mozdarani H, Akhlagpour S, Froughizadeh M: Radioprotective effects of 2-imino -3 (chromone-2-yl) carbonyl thiazolidine against gamma irradiation in mice. J Radiat Res 43:293–300, 2002PubMedCrossRefGoogle Scholar
  7. 7.
    Jagetia GC, Baliga MS, Venkatesh P, Ulloor JN: Influence of ginger rhizome (Zingiber officinalis Rosc) on survival, glutathione and lipid peroxidation in mice after whole-body exposure to gamma radiation. RadiatRes 160: 584–592, 2003Google Scholar
  8. 8.
    Landauer MR, Castro CA, Benson KA, Hogan JB, Weiss JF: Radioprotective and locomotor responses of mice treated with nimodipine alone and incombination with WR-151327. J Appl Toxicol 21: 25–31, 2001PubMedCrossRefGoogle Scholar
  9. 9.
    Pavlatos AM, Fultz O, Monberg MJ, Vootkur A: Review of oxymetholone: a 17α-alkylated anabolic-androgenic steroid. Clin Ther 23: 789–801,2001PubMedCrossRefGoogle Scholar
  10. 10.
    Hengge UR, Stocks K, Wiehler H, Faulkner S, Esser S, Lorenz C, Jentzen W, Hengge D, Goos M, Dudley RE, Ringham G: Double-blind, randomized, placebo-controlled phase III trial of oxymetholone for the treatment of HIVwasting. AIDS 28: 699–710, 2003CrossRefGoogle Scholar
  11. 11.
    Bolton S: Statistical inference: estimation and hypothesis testing In: Pharmaceutical Statistics Practical and Clinical Applications 3th Edition,Eds. J. Swarbrick, Inc, Marcel Dekker, New York, pp.162–178, 1997Google Scholar
  12. 12.
    Mauch P, Constine L, Greenberger J, Knospe W, Sullivan W, Liesveld JL, Deeg HJ: Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy. Int J Radiat Biol Oncol Biol Phys 31:1319–1339, 1995CrossRefGoogle Scholar
  13. 13.
    Dainiak N: Hematological consequences of exposure to ionizing radiation.Exp Hematol 30: 513–528, 2002PubMedCrossRefGoogle Scholar
  14. 14.
    Herodin F, Bourin P, Mayol JF, Lataillade JJ, Drouet M: Short-term injection of antiapoptotic cytokine combinations soon after lethal γ-irradiation promotes survival. Blood 101: 2609–2616, 2003PubMedCrossRefGoogle Scholar
  15. 15.
    Lord B., Hendry, JH: Radiation toxicology: bone marrow and leukemia. In: Radiation toxicology: bone marrow and leukemia. (J. H. Lord, Eds), Taylor& Francis, London, pp. 1–21, 1995Google Scholar
  16. 16.
    Patchen ML: Single and combination cytokine therapies for the treatmentof radiation-induced hematopoietic injury. Adv Biosci 94: 21–36, 1996Google Scholar
  17. 17.
    Neta R: Modulation of radiation damage by cytokines. Stem Cells Dayt 15:87–94, 1997PubMedCrossRefGoogle Scholar
  18. 18.
    Whitnall MH, Wilhelmsen CL, Mckinney L, Miner V, Seed TM, Jackson WE: Radioprotective efficacy and acute toxicity of 5-androstenediol after subcutaneous or oral administration in mice. Immunopharm Immunotoxicol 24:595–626, 2002CrossRefGoogle Scholar
  19. 19.
    Song JY, Han SK, Bae KG, Lim DS, Son SJ, Jung IS, Yi SY, Yun YS: Radioprotective effects of Ginsan, an immunomodulator. Radiat Res 159:768–774, 2003PubMedGoogle Scholar
  20. 20.
    Shahidi NT: A review of the chemistry, biological, action, and clinicalapplications of anabolic-androgenic steroids. Clin Ther 23:1355–1384, 2001PubMedCrossRefGoogle Scholar
  21. 21.
    Shahidi NT: Androgen and erythropoiesis. N Engl J Med 289: 72–80, 1973PubMedCrossRefGoogle Scholar
  22. 22.
    Kim SW, Hwang JH, Cheon JM, Park NS, Park SE, Park SJ, Yun HJ, Kim S, Jo DY. Direct and indirect effects of androgens on survival of hematopoieticprogenitor cells in vitro. J Korean Med Sci 20: 409–416, 2005PubMedCrossRefGoogle Scholar
  23. 23.
    Pamujula S, Graves RA, Freeman T, Srinivasan V, Bostanian LA, Kishore V, Mandal TK: Oral delivery of spray dried PLGA/amifostine nanoparticles. JParm Pharmacol 56: 1119–1125, 2004CrossRefGoogle Scholar
  24. 24.
    National Toxicology Program.: NTP Toxicology and Carcinogenesis Studies of Oxymetholone (CAS NO. 434-07-1) in F344/N Rats and Toxicology Studies of Oxymetholone in B6C3F1 Mice (Gavage Studies). Natl Toxicol Program Tech RepSer 485: 1–233, 1995Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Seyed Jalal Hosseinimehr
    • 1
    Email author
  • Valiallah Zakaryaee
    • 2
  • Mohsen Froughizadeh
    • 2
  1. 1.Department of Medicinal Chemistry, Faculty of PharmacyMazandaran University of Medical SciencesSariIran
  2. 2.Novin Medical Radiation InstituteTehranIran

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