title: In Vivo Protective Effects of Diosgenin against Doxorubicin-Induced Cardiotoxicity.
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.
authors.affiliation: School of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan. thomas.chen@unitybiotech.com.
authors.forename: Chih-Tai
authors.initials: CT
authors.lastname: Chen
authors.affiliation: Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung City 40402, Taiwan. rover_wang@hotmail.com.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: School of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan. king@csmu.edu.tw.
authors.forename: Cheng-Chin
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan. linhh@csmu.edu.tw.|Clinical Laboratory, Chung Shan Medical University, Taichung City 40201, Taiwan. linhh@csmu.edu.tw.
authors.forename: Hui-Hsuan
authors.initials: HH
authors.lastname: Lin
authors.affiliation: School of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan. cjh0828@csmu.edu.tw.|Clinical Laboratory, Chung Shan Medical University, Taichung City 40201, Taiwan. cjh0828@csmu.edu.tw.
authors.forename: Jing-Hsien
authors.initials: JH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D009202:Cardiomyopathies / Q000188:drug therapy; D066126:Cardiotoxicity / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D027742:Dioscorea / Q000737:chemistry; D004144:Diosgenin / Q000494:pharmacology*; D004317:Doxorubicin / Q000009:adverse effects*; D005979:Glutathione Peroxidase / Q000097:blood; D006339:Heart Rate; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D004144:Diosgenin
keywords: antioxidant; cGMP; cadiotoxicity; diosgenin; doxorubicin