Protective Effects of Salidroside on Epirubicin-Induced Early Left Ventricular Regional Systolic Dysfunction in Patients with Breast Cancer
Salidroside [2-(4-hydroxyphenyl)ethyl-β-D-glucopyranoside], one of the most potent ingredients extracted from the plant Rhodiola rosea L., has been shown to have a cardiovascular protective effect as an antioxidant, and early treatment of epirubicin-induced cardiotoxicity has been the focus of clinical chemotherapy in patients with breast cancer. However, the cardioprotective effects of salidroside on epirubicin-induced cardiotoxicity, especially early left ventricular regional systolic dysfunction, have to date been sparsely investigated.
The aim of this study was to investigate the protective effects of salidroside in preventing early left ventricular regional systolic dysfunction induced by epirubicin.
Sixty patients with histologically confirmed breast cancer were enrolled. Eligible patients were randomized to receive salidroside (600 mg/day; n= 30) or placebo (n = 30) starting 1 week before chemotherapy. Patients were investigated by means of echocardiography and strain rate (SR) imaging. We also measured plasma concentrations of reactive oxygen species (ROS). All parameters were assessed at baseline and 7 days after each new epirubicin dose of 100 mg/m2.
A decline of the SR peak was observed at an epirubicin dose of 200 mg/m2, with no significant differences between salidroside and placebo (1.35 ± 0.36 vs 1.42 ± 0.49/second). At growing cumulative doses of epirubicin, the SR normalized only with salidroside, showing a significant difference in comparison with placebo at epirubicin doses of 300 mg/m2 (1.67 ± 0.43 vs 1.32 ± 0.53/second, p< 0.05) and 400 mg/m2 (1.68±0.29 vs 1.40 ± 0.23/second, p < 0.05). Moreover, a significant increase in plasma concentrations of ROS was found with placebo, but they remained unchanged with salidroside.
Salidroside can provide a protective effect on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.
- Minotti G, Menna P, Salvatorelli E, et al. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004; 56: 185–229. CrossRef
- Elliott P. Pathogenesis of cardiotoxicity induced by anthracyclines. Semin Oncol 2006; 33: S2–7. CrossRef
- Zhou X, Wu Y, Wang X, et al. Salidroside production by hairy roots of Rhodiola sachalinens is obtained after transformation with Agrobacterium rhizogenes. Biol Pharm Bull 2007; 30: 439–42. CrossRef
- Wu T, Zhou H, Jin Z, et al. Cardioprotection of salidroside from ischemia/reperfusion injury by increasing N-acetylglucosamine linkage to cellular proteins. Eur J Pharmacol 2009; 613: 93–9. CrossRef
- Mercuro G, Cadeddu C, Piras A, et al. Early epirubicin-induced myocardial dysfunction revealed by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers. Oncologist 2007; 12: 1124–33. CrossRef
- Mantovani G, Maccio A, Madeddu C, et al. Quantitative evaluation of oxidative stress, chronic inflammatory indices and leptin in cancer patients: correlation with stage and performance status. Int J Cancer 2002; 98: 84–91. CrossRef
- Jensen BV, Skovsgaard T, Nielsen SL. Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol 2002; 13: 699–709. CrossRef
- Mantovani G, Madeddu C, Cadeddu C, et al. Persistence, up to 18 months of follow-up, of epirubicin-induced myocardial dysfunction detected early by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers. Oncologist 2008; 13: 1296–305. CrossRef
- Jassal DS, Han SY, Hans C, et al. Utility of tissue Doppler and strain rate imaging in the early detection of trastuzumab and anthracycline mediated cardiomyopathy. J Am Soc Echocardiogr 2009; 22: 418–24. CrossRef
- Ferreira AL, Matsubara LS, Matsubara BB. Anthracycline-induced cardiotoxicity. Cardiovasc Hematol Agents Med Chem 2008; 6: 278–81. CrossRef
- Zweier JL, Talukder MAH. The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res 2006; 70: 181–90. CrossRef
- Becker LB. New concepts in reactive oxygen species and cardiovascular reperfusion physiology. Cardiovasc Res 2004; 61: 461–70. CrossRef
- Halliwell B, Aruoma OI. DNA damage by oxygen-derived species: its mechanism and measurement in mammalian systems. FEBS Lett 1991; 281: 9–19. CrossRef
- Zhu YZ, Huang SH, Tan BKH, et al. Antioxidants in Chinese herbal medicines: a biochemical perspective. Nat Prod Rep 2004; 21: 478–89. CrossRef
- Zhong H, Xin H, Wu LX, et al. Salidroside attenuates apoptosis in ischemic cardiomyocytes: a mechanism through a mitochondria-dependent pathway. J Pharmacol Sci 2010; 114: 399–408. CrossRef
- Schriner SE, Abrahamyan A, Avanessian A, et al. Decreased mitochondrial superoxide concentrations and enhanced protection against paraquat in Drosophila melanogaster supplemented with Rhodiola rosea. Free Radic Res 2009; 43: 836–43. CrossRef
- Schriner SE, Avanesian A, Liu YX, et al. Protection of human cultured cells against oxidative stress by Rhodiola rosea without activation of antioxidant defenses. Free Radic Biol Med 2009; 47: 577–84. CrossRef
- Shen WS, Gao CH, Zhang H, et al. Effect of Rhodiola on serum troponin 1, cardiac integral backscatter and left ventricle ejection fraction of patients who received epirubicin-contained chemotherapy. Chin J Integr Trad West Med 2010; 12: 1250–2.
- Hu X, Zhang X, Qiu S, et al. Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells. Biochem Biophys Res Commun 2010; 398: 62–7. CrossRef
- Protective Effects of Salidroside on Epirubicin-Induced Early Left Ventricular Regional Systolic Dysfunction in Patients with Breast Cancer
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Drugs in R&D
Volume 12, Issue 2 , pp 101-106
- Cover Date
- Print ISSN
- Online ISSN
- Springer International Publishing
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Department of Echocardiography, Affiliated Jiangyin Hospital of Southeast University Medical College, 163 Shou-Shan Road, Jiangyin, Jiangsu, 214400, People’s Republic of China
- 2. Department of Oncology, Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu, People’s Republic of China