An antineoplastic agent
Hydroxyurea is a cell apoptosis inducer that inhibit DNA synthesis through inhibition of ribonucleotide reductase.
Hydroxyurea is used in a number of myeloproliferative, neoplastic, HIV, and non-hematological diseases[1]. Treatment of cells in primary culture with 30 μM hydroxyurea for 96 hours significantly increases the fractional HbF content. The Gγ: Aγ-globin mRNA is induced 0.30- to 8-fold in vitro[2]. Hydroxyurea has been shown to block HIV-1 reverse transcription and/or replication in quiescent peripheral blood mononuclear cells and macrophages[3].
Hydroxyurea therapy producs consistent reductions in WBC and ANC without improvement in anemia over 17 weeks. Hydroxyurea at 50mg/kg produces a reduced white blood cell count, absolute neutrophil count and no improvement in anemia compared to vehicle treated sickle cell mice[4].
参考文献:
[1]. Kovacic P, et al. Hydroxyurea (therapeutics and mechanism): metabolism, carbamoyl nitroso, nitroxyl, radicals, cell signaling and clinical applications. Med Hypotheses. 2011 Jan;76(1):24-31.
[2]. Watanapokasin Y, et al. In vivo and in vitro studies of fetal hemoglobin induction by hydroxyurea in beta-thalassemia/hemoglobin E patients. Exp Hematol. 2005 Dec;33(12):1486-92.
[3]. Lori F, et al. Rationale for the use of hydroxyurea as an anti-human immunodeficiency virus drug. Clin Infect Dis. 2000 Jun;30 Suppl 2:S193-7.
[4]. Lebensburger JD, et al. Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model. Haematologica. 2010 Sep;95(9):1599-603.
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Animal experiment: |
Mice: To determine whether hydroxyurea would improve anemia and/or prevent or diminish the development of organ damage in the absence of HbF induction, hydroxyurea, at doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg, or vehicle is administered five days per week to SCD mice[4]. |
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参考文献: [1]. Kovacic P, et al. Hydroxyurea (therapeutics and mechanism): metabolism, carbamoyl nitroso, nitroxyl, radicals, cell signaling and clinical applications. Med Hypotheses. 2011 Jan;76(1):24-31. |
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