salvianolic-acid-B and Heart-Diseases

Cardiovascular complications have been well documented as the downside to conventional cancer chemotherapy. As a notable side effect of cisplatin (CDDP), cardiotoxicity represents a major obstacle to the successful treatment of cancer. It has been reported that Salvianolic acid B (SalB) possesses cardioprotective quality. However, the effect of SalB on cardiac damage caused by conventional cancer chemotherapy remains unclear. In this study, we clarified the protective effect of SalB on cisplatin-induced heart injury. Furthermore, in H9c2 cells, SalB dramatically reduced cisplatin-induced apoptosis and oxidative stress by modulating the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway. In conclusion, SalB had great potential in mitigating cisplatin-induced cardiac injury. Furthermore, more attention should be placed on natural active compounds containing SalB with antioxidant effects for the treatment of cardiomyopathy.

Topics: Animals; Antineoplastic Agents; Antioxidants; Benzofurans; Cell Line; Cell Survival; Cisplatin; Creatine Kinase, MB Form; Heart; Heart Diseases; Heme Oxygenase-1; L-Lactate Dehydrogenase; Male; Mice, Inbred C57BL; Myocardium; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Oxidative Stress; Rats; Signal Transduction; Stroke Volume

Doxorubicin (DOX)-induced cardiotoxicity is a clinically complex syndrome that leads to significant pain to cancer survivors. Endoplasmic reticulum (ER) stress has been suggested to be an important contributor to myocardium dysfunction during this phenomenon. Our previous study proved that Salvianolic acid B (Sal B) protected against doxorubicin induced cardiac dysfunction by inhibiting ER stress and cardiomyocyte apoptosis. However, the underlying molecular mechanism is not yet clearly. In this study, we investigated the protective effect and mechanisms of Sal B againest DOX-induced cardiac injury and ER stress in vivo and in vitro. After pretreatment with Sal B (0.25, 0.5, 1mg/kg i.v.) for 7 days, male SD rats were intraperitoneally injected with a single dose of DOX (3mg/kg) every 2 days for three injections. The cardioprotective effect of Sal B was observed 2 weeks after the first administration. Adult rat ventricular myocytes were isolated and treated with Sal B (20μg/ml) for 6h and then exposed in DOX (1μm) for 4h. The cardiomyocyte contractility and the level of intracellular Ca

Topics: Animals; Apoptosis; Benzofurans; Calcium Signaling; Cardiotoxicity; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Doxorubicin; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Heart Diseases; Male; Membrane Potential, Mitochondrial; Myocardial Contraction; Myocytes, Cardiac; Protective Agents; Rats, Sprague-Dawley; Time Factors; TRPC Cation Channels

Although doxorubicin is an effective antitumor agent, the serious cardiotoxicity mediated by the production of reactive oxygen species has remained a considerable clinical problem. In China, salvianolic acids has been widely used for cardioprotection. To test whether salvianolic acids holds the potential to be protective against cardiotoxicity of doxorubicin, we created an acute cardiac injury mice model. Therapeutic treatment with salvianolic acids (40 mg/kg for 3 connective days) significantly reduced doxorubicin-induced (15 mg/kg) toxicity, including elevation of body weight and heart weight/tibia length ratio, decrease of creatine kinase, improvement of electrocardiography and heart vacuolation. Furthermore, the antioxidative effects of salvianolic acids were verified by oxygen radicals absorbance capacities assay in vitro and malondialdehyde detection in vivo, suggesting one possible mechanism of salvianolic acids on cardioprotection through blocking oxidative stress.

Topics: Animals; Antibiotics, Antineoplastic; Benzofurans; Body Weight; Caffeic Acids; Cardiotonic Agents; Creatine Kinase; Doxorubicin; Electrocardiography; Heart Diseases; Lactates; Male; Malondialdehyde; Mice; Myocardium; Oxidative Stress; Reactive Oxygen Species; Tissue Fixation