Our findings also showed that a significant rise in ROS concentrations continued throughout epirubicin chemotherapy. Although the pathogenesis of epirubicin-induced cardiotoxicity remains controversial, the oxidative stress-based hypothesis has gained the widest acceptance.[10] Robust generation of ROS is defined as oxidative stress, and significant increases in generation of ROS (a collective name for hydrogen peroxide, superoxide, and hydroxyl radicals) in cardiomyocytes, as well as serum concentrations, have been reported in epirubicin-induced cardiotoxicity.[10,11] ROS

are excessively generated from a likely mitochondrial source, then hasten lipid peroxidation and DNA damage, and consequently initiate cell apoptosis or necrosis.[12,13] Accordingly, successful antioxidant interventions BI 6727 targeted to reduce ROS offer insights into preventing epirubicin-induced cardiotoxicity. Rhodiola rosea has long been used as an adaptogen in traditional Tibetan high throughput screening compounds medicine.[14] Salidroside [2-(4-hydroxyphenyl)ethyl-β-D-glucopyranoside], the main active compound of Rhodiola plants, is reported to possibly play a central role in alleviation of mitochondrial-generated ROS and modulation of mitochondrial-related apoptosis signaling in multiple types of cells.[15] More recently, in vitro

analysis showed that pretreatment with salidroside exerted remarkable benefits in inhibition of ROS overgeneration as an antioxidant,

and decreased mitochondrial superoxide concentrations.[16] Salidroside supplementation could protect cultured cells against ultraviolet light, paraquat, and H2O2.[17] In the present study, an early ΔSR derived from DTI parameters observed after an epirubicin these dose of 200 mg/m2 was accompanied in the placebo group by a significant increase in ROS serum concentrations, which seems to confirm the relationship between a ROS increase and epirubicin-induced early left ventricular systolic regional dysfunction. Safety assessments of salidroside have been reported in our earlier study.[18] Adverse events were spontaneously reported by the investigator at the end of the study. The investigator made the decision about whether an abnormality represented an adverse event. There were no clinical adverse events throughout the period of salidroside therapy. The small number of patients enrolled and the short follow-up are some of the limitations of the present study. Moreover, DTI-derived strain measurements are dependent on the direction of the Doppler angle of incidence in relation to myocardial motion. This limitation could be overcome by a new measure of two-dimensional strain, using speckle tracking echocardiography, in a further study. Recent studies have shown that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.