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Davallialactone protects against adriamycin-induced cardiotoxicity in vitro and in vivo

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Abstract

Adriamycin (ADR) is a potent anticancer drug. Its clinical applications are limited due to its cardiotoxicity. Oxidative stress is responsible for cardiomyopathy induced by ADR. Previous studies have demonstrated that davallialactone (DAVA), extracted from mushroom Inonotus xeranticus, has potential antiplatelet aggregation activity and free radical scavenging properties. In this study, we investigated whether DAVA has protective effects against ADR-induced free radical accumulation and apoptosis in cardiac muscle cells and compared the effects of DAVA with N-acetylcysteine, a potent antioxidant. We evaluated the effect of DAVA on ADR-induced cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and crystal violet staining, the reactive oxygen species (ROS) production by flow cytometry, and the expression of stress-related proteins like Cu/Zn superoxide dismutase (SOD), Mn-SOD, and the involvement of mitogen-activated protein kinase pathway by Western blot analysis. Apoptosis was assessed by nuclear condensation and the expression levels of pro-apoptotic proteins, such as caspase-3 and polyadenosine diphosphate-ribose polymerase (PARP). The cardio-protective effects of DAVA were also evaluated in an in vivo study in an animal model of ADR-induced acute cardiomyopathy. Our results showed that DAVA significantly increased the viability of doxorubicin-injured H9c2 cells and inhibited ADR-induced ROS production, apoptosis, and the expression of Cu/Zn SOD and Mn-SOD. DAVA also inhibited the expression of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), which was activated by ADR. In the in vivo animal model, treatment involving DAVA significantly reduced cardiomyocyte lesions. These results suggest that DAVA is a potentially protective agent for ADR-induced cardiotoxicity in cardiomyocytes and can be a potential candidate to protect against cardiotoxicity in ADR-treated cancer patients.

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Acknowledgments

The authors thank Professor S. Kamala-Kannan for the careful review of the manuscript and revision suggestions. This study was supported by a grant from the Korea Forest Service (S121010L090120) and in part by a grant of the Clinical Trial Center for Functional Foods of Chonbuk National University Hospital.

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Authors and Affiliations

  1. Department of Pediatrics, Chonbuk National University Hospital, 634-18 Keumam-dong, Jeonju, 561-712, Republic of Korea

    Sankarganesh Arunachalam, Sun Young Kim, Min Sun Kim & Pyoung Han Hwang

  2. Research Institute of Clinical Medicine, Chonbuk National University, Jeonju, 561-712, Republic of Korea

    Sankarganesh Arunachalam, Sun Young Kim & Pyoung Han Hwang

  3. Division of Cardiology, Department of Internal Medicine, School of Medicine, Chonbuk National University, Jeonju, 561-712, Republic of Korea

    Sun Hwa Lee

  4. Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju, 561-712, Republic of Korea

    Young Hee Lee & Ho Keun Yi

  5. Division of Biotechnology, College of Environmental and Bioresources Sciences, Chonbuk National University, Jeonju, 561-712, Republic of Korea

    Bong Sik Yun

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  1. Sankarganesh Arunachalam
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  2. Sun Young Kim
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Correspondence to Pyoung Han Hwang.

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Arunachalam, S., Kim, S.Y., Lee, S.H. et al. Davallialactone protects against adriamycin-induced cardiotoxicity in vitro and in vivo. J Nat Med 66, 149–157 (2012). https://doi.org/10.1007/s11418-011-0567-1

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  • DOI: https://doi.org/10.1007/s11418-011-0567-1

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