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.

Cardioprotective Potential of Murraya koenigii (L.) Spreng. Leaf Extract against Doxorubicin‐Induced Cardiotoxicity in Rats

“…Consistent to the results that we reported, Asfar et al also reported that doxorubicin treatment decreased the activities of antioxidant enzymes and Acacia hydaspica leaf extract that has the potential to increase GSH, GPx, and GR level which was attributed by polyphenolic constituents and antioxidant properties of this leaf extract [50]. A study done by Chen et al has shown that diosgenin, a steroidal saponin of Dioscorea opposita, also has the ability to increase the GSH and GPx level decreased by doxorubicin treatment in Balb/c mice [48]. ymoquinone, an active constituent of Nigella sativa, having antioxidant and anti-inflammatory actions was also shown to protect against doxorubicin-induced cardiotoxicity in mice with increased value of antioxidant markers including GSH, GPx, and GR activities [52].…”

“…According to the results of the present study, elevated AST and LDH levels were significantly reduced by the pretreatment with aqueous plant extract compared to the doxorubicin control. Many previous studies have also shown that compounds with antioxidant property may bring down the cardiac biomarkers in rats treated with doxorubicin [47][48][49].…”

Ca2+ Entry, Oxidative Stress, Ceramide and Suicidal Erythrocyte Death Following Diosgenin Treatment

“…Diosgenin, a bioactive steroid sapogenin from legumes and yams [1][2][3][4], has anticancer, cardiovascular protective, anti-diabetes, neuroprotective, immunomodulatory, estrogenic, and skin protective potency [1][2][3][4][5][6][7][8][9][10][11][12][13]. Moreover, diosgenin may foster male fertility [14].…”

Saponins as chemosensitizing substances that improve effectiveness and selectivity of anticancer drug—Minireview of in vitro studies

“…Its effects may also be associated with the inhibition of topoisomerase II, free radical formation, and finally induction of the apoptosis process (Swift, Rephaeli, Nudelman, Phillips, & Cutts, ). DOX is most effective in the S and G2 phases of the cell cycle; its therapeutic utility is limited by cardiotoxicity (Chen, Wang, Hsu, Lin, & Chen, ) and nephrotoxicity (Su et al, ). Cellular injury induced by DOX may involve lipid peroxidation, changes in adenylate cyclase activity, and ROS formation (Chen et al, ), which finally leads to DOX‐induced apoptosis and inflammation.…”

“…DOX is most effective in the S and G2 phases of the cell cycle; its therapeutic utility is limited by cardiotoxicity (Chen, Wang, Hsu, Lin, & Chen, ) and nephrotoxicity (Su et al, ). Cellular injury induced by DOX may involve lipid peroxidation, changes in adenylate cyclase activity, and ROS formation (Chen et al, ), which finally leads to DOX‐induced apoptosis and inflammation.…”