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In Vivo Protective Effects of Diosgenin against Doxorubicin-Induced Cardiotoxicity.

Chen CT, Wang ZH, Hsu CC, Lin HH, Chen JH - Nutrients (2015)

Bottom Line: 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.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 Article: PubMed Central - PubMed

Affiliation: School of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan. thomas.chen@unitybiotech.com.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of diosgenin on levels of cAMP and cGMP (A), and mRNA expressions of PDE5A and PDE3A (B) in heart tissues of mice treated with DOX for four weeks. Values are mean ± SD, n = 10. a,b Means in a row without a common letter differ, p < 0.05.
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nutrients-07-04938-f001: Effect of diosgenin on levels of cAMP and cGMP (A), and mRNA expressions of PDE5A and PDE3A (B) in heart tissues of mice treated with DOX for four weeks. Values are mean ± SD, n = 10. a,b Means in a row without a common letter differ, p < 0.05.

Mentions: It is well known that cGMP exerts its effects by interacting with PDE, and cGMP-dependent signaling plays an important protective role in cardiac injury [14,15]. As compared with the control, treatment with DOX decreased the levels of cAMP and cGMP in the heart, especially the later (p < 0.05) (Figure 1A). Diosgenin augmented the cGMP and cAMP levels as compared with DOX alone (p < 0.05). Moreover, the cardiac mRNA expression of PDE5A was increased after a four-week treatment of DOX, whereas that of PDE3A was slightly affected. Treatment with diosgenin also attenuated both mRNA expressions compared to DOX alone (p < 0.05) (Figure 1B).


In Vivo Protective Effects of Diosgenin against Doxorubicin-Induced Cardiotoxicity.

Chen CT, Wang ZH, Hsu CC, Lin HH, Chen JH - Nutrients (2015)

Effect of diosgenin on levels of cAMP and cGMP (A), and mRNA expressions of PDE5A and PDE3A (B) in heart tissues of mice treated with DOX for four weeks. Values are mean ± SD, n = 10. a,b Means in a row without a common letter differ, p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488824&req=5

nutrients-07-04938-f001: Effect of diosgenin on levels of cAMP and cGMP (A), and mRNA expressions of PDE5A and PDE3A (B) in heart tissues of mice treated with DOX for four weeks. Values are mean ± SD, n = 10. a,b Means in a row without a common letter differ, p < 0.05.
Mentions: It is well known that cGMP exerts its effects by interacting with PDE, and cGMP-dependent signaling plays an important protective role in cardiac injury [14,15]. As compared with the control, treatment with DOX decreased the levels of cAMP and cGMP in the heart, especially the later (p < 0.05) (Figure 1A). Diosgenin augmented the cGMP and cAMP levels as compared with DOX alone (p < 0.05). Moreover, the cardiac mRNA expression of PDE5A was increased after a four-week treatment of DOX, whereas that of PDE3A was slightly affected. Treatment with diosgenin also attenuated both mRNA expressions compared to DOX alone (p < 0.05) (Figure 1B).

Bottom Line: 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.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 Article: PubMed Central - PubMed

Affiliation: School of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan. thomas.chen@unitybiotech.com.

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.

No MeSH data available.


Related in: MedlinePlus