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In Vivo Protective Effects of Diosgenin against Doxorubicin-Induced Cardiotoxicity

School of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan
Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung City 40402, Taiwan
School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan
Clinical Laboratory, Chung Shan Medical University, Taichung City 40201, Taiwan
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2015, 7(6), 4938-4954;
Received: 24 April 2015 / Revised: 30 May 2015 / Accepted: 8 June 2015 / Published: 17 June 2015
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
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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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