Salidroside improves doxorubicin-induced cardiac dysfunction by suppression of excessive oxidative stress and cardiomyocyte apoptosis
| Autor: | Xiao-Xiao Wang, Xue Wang, Ye Zhu, Wei Jiang, Zhiyun Guo, Xu-Lei Wang, Ping Li, Lili Xiong, Jia-Xiang Chen, Hua-Li Chen, Ruli Li |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cardiotonic Agents Cell Survival Heart Ventricles Apoptosis Pharmacology medicine.disease_cause Antioxidants Gene Expression Regulation Enzymologic Cell Line chemistry.chemical_compound Mice Random Allocation Glucosides Phenols medicine Ventricular Dysfunction Animals Doxorubicin Myocytes Cardiac Viability assay Cell Size Cardiotoxicity Antibiotics Antineoplastic biology Chemistry Salidroside Clone Cells Rats Mice Inbred C57BL Oxidative Stress Catalase NOX1 biology.protein Cardiology and Cardiovascular Medicine Oxidoreductases Oxidative stress medicine.drug |
| Zdroj: | Journal of cardiovascular pharmacology. 62(6) |
| ISSN: | 1533-4023 |
| Popis: | Doxorubicin (DOX) is a potent available antitumor drug; however, its clinical use is limited by the cardiotoxicity. Salidroside (SLD), with strong antioxidative and cytoprotective actions, is of particular interest in the development of antioxidative therapies for oxidative injury in cardiac diseases. Now, the protection and underlying mechanisms of SLD against DOX-induced cardiotoxicity are still unknown. In the present study, we revealed both antioxidative mechanism and Bcl2-dependent survival signaling involved in SLD's protection. We observed that DOX exposure induced mortality elevation, body weight loss, and cardiac dysfunction in mice, increased lactate dehydrogenase leakage and cardiomyocyte apoptosis, but decreased cell viability and size in cardiac tissues and cultured H9c2 cells, respectively, which were effectively antagonized by SLD supplement. We further observed that SLD significantly reduced the intercellular oxidative stress level, partly by inhibiting NOX1 expression and augmenting the expression and activities of the endogenous antioxidative enzymes, catalase, and manganese superoxide dismutase. In addition, SLD treatment upregulated the antiapoptotic Bcl2 and downregulated the proapoptotic Bax and inhibited a downstream pathway of Bcl2/Bax and caspase-3 activity. Our results indicated that SLD effectively protected the cardiomyocytes against DOX-induced cardiotoxicity by suppressing the excessive oxidative stress and activating a Bcl2-mediated survival signaling pathway. |
| Databáze: | OpenAIRE |
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