Accelerated recovery from gamma-irradiation-induced leukopenia in mice by the biscoclaurine alkaloid, Cepharanthin--comparison with recombinant human granulocyte colony-stimulating factor.
The effect of a biscoclaurine alkaloid drug, Cepharanthin (CE), on recovery from severe leukopenia induced by whole body gamma-irradiation at a dose of 3 Gy, was compared with that of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Daily intraperitoneal administration of 100 micrograms CE into the irradiated mice significantly prevented decrease of leukocyte numbers in the peripheral blood and accelerated recovery from leukopenia to normal. The activity of CE was somewhat weaker than that of 20,000 units of rhG-CSF when administered daily subcutaneously. In cell composition of peripheral leukocytes, CE increased the numbers of polymorphonuclear (PMN) cells and lymphocytes compared with those of the irradiated controls. Stronger change in PMN cell numbers than with CE was induced by administration of rhG-CSF. No significant increment of the activity to form colonies in spleen (colony-forming unit in spleen; CFU-S) was observed in bone marrow cells from irradiated donor mice administered CE, though CE induced CSF production into sera. Administration of rhG-CSF stimulated the CFU-S activity. These results indicate that CE increased recruitment of PMN cells from the marginal pool rather than the stimulation of pluripotent stem cells in the bone marrow.
Kumazawa
Y
Y
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Kaneko
M
M
Inagaki
K
K
Matsuzaki
N
N
Nomoto
K
K
D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D044182:Benzylisoquinolines; D001853:Bone Marrow / Q000502:physiology / Q000528:radiation effects; D001854:Bone Marrow Cells; D003115:Colony-Stimulating Factors / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007962:Leukocytes / Q000528:radiation effects; D007970:Leukopenia / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D011833:Radiation Injuries, Experimental / Q000188:drug therapy; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D052117:Benzodioxoles
D000470:Alkaloids; D044182:Benzylisoquinolines; D003115:Colony-Stimulating Factors; D016179:Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; C006947:cepharanthine; D052117:Benzodioxoles