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.
Luo
ZhongGuang
Z
Shanghai Institute of Hematology, School of Medicine, Shanghai Jiao Tong University, Shanghai 20001, China.
Zhong
Lu
L
Han
XiaoFeng
X
Wang
HaiRong
H
Zhong
JiHua
J
Xuan
ZhengHua
Z
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D027885:Astragalus propinquus / Q000737:chemistry*; D002478:Cells, Cultured; D003630:Daunorubicin / Q000009:adverse effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D000111:Acetylcysteine; D003630:Daunorubicin