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Nutrients 2015, 7(6), 4938-4954; doi:10.3390/nu7064938

In Vivo Protective Effects of Diosgenin against Doxorubicin-Induced Cardiotoxicity

1
School of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan
2
Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung City 40402, Taiwan
3
School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan
4
Clinical Laboratory, Chung Shan Medical University, Taichung City 40201, Taiwan
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 24 April 2015 / Revised: 30 May 2015 / Accepted: 8 June 2015 / Published: 17 June 2015
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Abstract

Doxorubicin (DOX) induces oxidative stress leading to cardiotoxicity. Diosgenin, a steroidal saponin of Dioscorea opposita, has been reported to have antioxidant activity. Our study was aimed to find out the protective effect of diosgenin against DOX-induced cardiotoxicity in mice. DOX treatment led to a significant decrease in the ratio of heart weight to body weight, and increases in the blood pressure and the serum levels of lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and creatine kinase myocardial bound (CK-MB), markers of cardiotoxicity. In the heart tissue of the DOX-treated mice, DOX reduced activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPx), were recovered by diosgenin. Diosgenin also decreased the serum levels of cardiotoxicity markers, cardiac levels of thiobarbituric acid relative substances (TBARS) and reactive oxygen species (ROS), caspase-3 activation, and mitochondrial dysfunction, as well as the expression of nuclear factor kappa B (NF-κB), an inflammatory factor. Moreover, diosgenin had the effects of increasing the cardiac levels of cGMP via modulation of phosphodiesterase-5 (PDE5) activity, and in improving myocardial fibrosis in the DOX-treated mice. Molecular data showed that the protective effects of diosgenin might be mediated via regulation of protein kinase A (PKA) and p38. Our data imply that diosgenin possesses antioxidant and anti-apoptotic activities, and cGMP modulation effect, which in turn protect the heart from the DOX-induced cardiotoxicity. View Full-Text
Keywords: doxorubicin; cadiotoxicity; diosgenin; antioxidant; cGMP doxorubicin; cadiotoxicity; diosgenin; antioxidant; cGMP
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Chen, C.-T.; Wang, Z.-H.; Hsu, C.-C.; Lin, H.-H.; Chen, J.-H. In Vivo Protective Effects of Diosgenin against Doxorubicin-Induced Cardiotoxicity. Nutrients 2015, 7, 4938-4954.

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