Astragalus membranaceus prevents daunorubicin-induced apoptosis of cultured neonatal cardiomyocytes: role of free radical effect of Astragalus membranaceus on daunorubicin cardiotoxicity.

Anthracyclines are antitumor antibiotics with significant activity against solid and hematologic malignancies. One problem preventing more widespread use has been the development of cardiotoxicity. To determine whether antioxidant agents can reduce the cardiotoxicity of anthracyclines, a herb Astragalus membranaceus was introduced, which has been widely used for the treatment of cardiovascular diseases in China and was confirmed to be an effective antioxidant agent recently. Pre-treatment with Astragalus membranaceus significantly attenuated the daunorubicin-induced increases of reactive oxygen species (p < 0.001), apoptosis (p < 0.05) and the secretions of LDH (p < 0.01) in cultured neonatal cardiomyocytes. Astragalus membranaceus also raised the EC(50) of daunorubicin 1.24-fold. Compared with Astragalus membranaceus, N-acetyl-L-cysteine had similar effects on daunorubicin-induced cell injury, however, superoxide dismutase reduced reactive oxygen species without attenuating apoptosis. The subcellular distribution of DNR was similar to the distribution of MitoTracker Red 580 in mitochondria, which was mainly in the cytoplasm around the nuclear membrane in cultured neonatal cardiomyocytes. In conclusion, the results suggested that Astragalus membranaceus is potentially protective against daunorubicin cardiotoxicity by decreasing free radical release and apoptosis in cultured neonatal cardiomyocytes. The main subcellular distribution of daunorubicin may be in the mitochondria.

[Effect of recombinant human granulocyte colony-stimulating factor on neutrophil morphology, function and phenotype in patients with acute leukemia undergoing chemotherapy].

This study was to explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophil morphology, function and phenotype in patients with acute leukemia undergoing chemotherapy. Neutrophil morphology was observed under microscope with oil immersion; phagocytotic function was examined by measuring the amount of hydrogen peroxide produced by neutrophil; chemotaxis was analyzed by agarose method; oxidative burst was analyzed by flow cytometry using immunofluorescence technique; neutrophil phenotype was analyzed by flow cytometry and immunofluorescence techniques. The results showed that after rhG-CSF administration, the increased "toxic" granulation, vacuoles and Döhle bodies were observed in neutrophils of patients with acute leukemia. Compared with normal control, the functions of phagocytosis, chemotaxis, oxidative burst of neutrophil were impaired after chemotherapy, while these functions were enhanced and returned to normal level or even to be exceeded after administration of rhG-CSF. In patients with acute leukemia the neutrophil presented significantly higher expression of CD64 and CD62L than that in normal control, and a mild increase of CD64 expression and significant increase of CD62L expression were found in patients after rhG-CSF treatment. No modifications of CD16, CD32, CD14 and CD11b expression were detected in these patients before or after G-CSF administration. It is concluded that rhG-CSF administration can modify the morphology, function and phenotype of neutrophils in the patients with acute leukemia undergoing chemotherapy, and these modifications of neutrophil behavior may be supposed to be a reason for the enhancement of organism anti-infection ability.