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Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment.

Abstract

The clinical application of doxorubicin (DOX) is compromised by its cardiac toxic effect. Cyclovirobuxine D (CVB-D) is a steroid alkaloid extracted from a traditional Chinese medicine, Buxus microphylla. Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations. By using TUNEL assay and western blot analysis, we found that CVB-D pretreatment reduced DOX-induced apoptosis of myocardial cells and mitochondrial cytochrome c release to cytosol. CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), as well as mitochondrial DNA copy number. These findings demonstrate that CVB-D protects against DOX-induced cardiomyopathy, at least in part, by suppression of oxidative damage and mitochondrial biogenesis impairment.

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  • Authors+Show Affiliations

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    Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, China ; Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China.

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    Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, China.

    ,

    Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, China.

    ,

    Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, China.

    ,

    Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, China.

    ,

    Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China.

    Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, China.

    Source

    MeSH

    Animals
    Apoptosis
    Cardiomyopathies
    Cytochromes c
    Doxorubicin
    Drugs, Chinese Herbal
    Glutathione Disulfide
    Lipid Peroxidation
    Mice, Inbred C57BL
    Mitochondria
    Myocardial Contraction
    Myocardium
    Organelle Biogenesis
    Oxidative Stress
    Protein Carbonylation

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    26075032

    Citation

    Guo, Qian, et al. "Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy By Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment." Oxidative Medicine and Cellular Longevity, vol. 2015, 2015, p. 151972.
    Guo Q, Guo J, Yang R, et al. Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment. Oxid Med Cell Longev. 2015;2015:151972.
    Guo, Q., Guo, J., Yang, R., Peng, H., Zhao, J., Li, L., & Peng, S. (2015). Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment. Oxidative Medicine and Cellular Longevity, 2015, p. 151972. doi:10.1155/2015/151972.
    Guo Q, et al. Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy By Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment. Oxid Med Cell Longev. 2015;2015:151972. PubMed PMID: 26075032.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment. AU - Guo,Qian, AU - Guo,Jiabin, AU - Yang,Rong, AU - Peng,Hui, AU - Zhao,Jun, AU - Li,Li, AU - Peng,Shuangqing, Y1 - 2015/05/14/ PY - 2014/11/04/received PY - 2015/02/11/revised PY - 2015/02/23/accepted PY - 2015/6/16/entrez PY - 2015/6/16/pubmed PY - 2016/4/5/medline SP - 151972 EP - 151972 JF - Oxidative medicine and cellular longevity JO - Oxid Med Cell Longev VL - 2015 N2 - The clinical application of doxorubicin (DOX) is compromised by its cardiac toxic effect. Cyclovirobuxine D (CVB-D) is a steroid alkaloid extracted from a traditional Chinese medicine, Buxus microphylla. Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations. By using TUNEL assay and western blot analysis, we found that CVB-D pretreatment reduced DOX-induced apoptosis of myocardial cells and mitochondrial cytochrome c release to cytosol. CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), as well as mitochondrial DNA copy number. These findings demonstrate that CVB-D protects against DOX-induced cardiomyopathy, at least in part, by suppression of oxidative damage and mitochondrial biogenesis impairment. SN - 1942-0994 UR - https://www.unboundmedicine.com/medline/citation/26075032/Cyclovirobuxine_D_Attenuates_Doxorubicin_Induced_Cardiomyopathy_by_Suppression_of_Oxidative_Damage_and_Mitochondrial_Biogenesis_Impairment_ L2 - https://dx.doi.org/10.1155/2015/151972 DB - PRIME DP - Unbound Medicine ER -