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Although the appearance of Doxil alleviated the cardiotoxicity of DOX, the progression-free survival of patients was not prolonged compared with traditional medication regimens, and side effects such as hand-foot syndrome has occurred. In order to solve this dilemma, we have designed a novel co-delivery strategy to construct a co-loaded liposome of berberine (BER) and doxorubicin (DOX), which was called LipoBeDo. The optimal synergistic ratio of the two drugs was screened by cell cytotoxicity experiments in vitro, and the optimal attenuation ratio was further determined by in vivo cardiac H&E staining pathological sections. The optimal combination treatment caused a robust increase in apoptotic cells of 4T1, as compared to drug alone treatment. The prepared co-loaded liposome, LipoBeDo, had high encapsulation efficiency and good stability. The nanoliposome carrier controlled the biological fate of the drugs and maintained a pre-defined optimal ratio in vivo. The LipoBeDo significantly inhibited tumor growth in 4T1 murine mammary carcinoma model compared with Doxil (P < 0.05), and completely overcame the myocardial rupture toxicity caused by Doxil in mice. Our co-loaded liposome delivery platform technology provided a new direction for the clinical treatment of triple-negative breast cancer and the safe application of DOX.

Background: The protective effects of silymarin on liver and heart have been investigated and identified by many researchers. This study evaluates the protective effects of this substance on hepatotoxicity and cardiotoxcity of chemotherapy drugs in leukemic children. Materials and Methods: In this study, 71 children, aging 2-14 years old, going through the maintenance phase of acute lymphoblastic leukemia (ALL) treatment at Children's Cancer Center of Isfahan University of Medical Sciences (Iran) in 2015 were studied. Two patients died and the remaining patients were divided into intervention and control groups. Intervention group received Mercaptopurin and Methotrexate plus Silymarin 140mg/day and control group were taking only Mercaptopurin and Methotrexate. Liver enzymes, Coagulation tests, Creatine kinase-Muscle and Brain (CK-MB), Ejection fraction and Systolic function (SF) were measured at the first, and 3 and 6 months' intervals from the commencement of study. The Data was analyzed by using SPSS and P = 0.05 was considered as statistically significant. Associations between variables were analyzed using independent t-test, chi square, and repeated measures ANOVA test. Results: Mean levels of Alanine aminotransferase in both groups increased significantly at 6 months interval (P=0.01, 0.01, for control and intervention groups respectively). Although increment was more among controls, there were no significant differences between the two groups (P= 0.85). Furthermore, Aspartate aminotransferase and Alkaline phosphatase increased in both groups and the increment was significant in the controls (P=0.001, 0.05, for control and intervention groups respectively). Coagulation tests prolonged in the first 3 months in both groups and the prolongation was more in control group. Changes in CK-MB were not significant in intervention and controls (P=0.07, 0.10, respectively) but ejection fraction and SF decreased in both groups, especially among controls. Conclusion: It seems that Silymarin can be useful in prevention of hepatotoxicity and cardiotoxcity of chemotherapy drugs for ALL children. [ABSTRACT FROM AUTHOR]

Doxorubicin is an anthracycline group antibiotic and has long been used as an antineoplastic agent. The most important side effect that limits the usage of doxorubicin is cardiotoxicity, which is observed at cumulative doses. We investigated the protective effect of clarithromycin that is known to have antioxidant and anti-inflammatory effects against Doxorubicin related cardiotoxicity. The aim of our study was to evaluate the effects of clarithromycin in the antioxidant enzyme status and myocardium of doxorobucine-treated rats. A total of 28 adult, male Wistar rats (200-250 g) were divided into 4 groups. Group I was the control group, rats in group 2 were administered doxorubicin, rats in group 3 were administered clarithromycin, and rats in group 4 were administered Doxorubicin + Clarithromycin. Following the scarification of all rats, antioxidant (glutathione) and oxidant (malodialdehyde) levels were measured in the cardiac tissue. Additionally, the cardiac muscles were evaluated histopathologically via hematoxylin eosin staining. The antioxidant amount (glutathione) was significantly higher in the treatment group compared to the doxorubicin group (p= 0.025), whereas the amount of oxidant (malondialdehyde) was significantly lower (p= 0.022). The histopathological examination revealed significant cardiotoxicity in the Doxorubicin group and significant reduction in the cardiotoxicity in the Doxorubicin + Clarithromycin group. The results obtained in this study provide evidence for the usefulness of the clarithromycin as a cardioprotective agent. [ABSTRACT FROM AUTHOR]

Doxorubicin is known to cause cardiomyopathy and congestive heart failure (CHF) upon chronic administration. A major obstacle to doxorubicin-containing multiagent therapies pertains to the possible development of cardiomyopathy and CHF at lower than expected cumulative doses of doxorubicin. For example, the cardiac toxicity of doxorubicin is aggravated by the anti-HER2 antibody Trastuzumab or by the tubulin-active taxane paclitaxel; however, the mechanisms by which Trastuzumab and paclitaxel aggravate doxorubicin-induced cardiotoxicity are mechanistically distinct: Trastuzumab interferes with cardiac-specific survival factors that help the heart to withstand stressor agents like anthracyclines, while paclitaxel acts by stimulating the formation of anthracycline metabolites that play a key role in the mechanism of cardiac failure. Here, we briefly review the molecular mechanisms of the cardiotoxic synergism of Trastuzumab or paclitaxel with doxorubicin, and we attempt to briefly outline how the mechanistic know-how translates into the clinical strategies for improving the safety of anthracycline-based multiagent therapies. [ABSTRACT FROM AUTHOR]

A translational safety biomarker for toxic myocardial injury is needed in drug discovery and development. This need reflects the increasing recognition of occurrence of cardiotoxicities, prior lack of preclinical blood biomarkers for toxic cardiac injury, introduction of troponin as a biomarker, and regulatory and industry drivers. Cardiac troponin is considered the gold-standard biomarker in humans for cardiac injury due to ischemic injury and drug toxicity. It has been demonstrated to correlate highly with histopathological extent of injury, degree of impairment of cardiac function, and prognosis. Numerous studies have now clearly demonstrated that both cardiac troponin T and cardiac troponin I are sensitive and specific biomarkers of cardiac injury in laboratory animals. Their use is highly recommended for incorporation into preclinical drug-safety studies, especially whenever there is any history of cardiac effect in prior studies with a compound of the same or similar chemical or pharmacological class. The main caveats with respect to cross-species use of specific cardiac troponin assays are the need for species-specific validation, definition of cut-offs based on relevant assessments of imprecision and reference ranges or concurrent controls, and knowledge of the species-dependent kinetics of release into, and clearance from, the blood. Future development of high-sensitivity assays should determine whether minimal increases below a threshold concentration of troponin might reflect reversible myocardial effects. [ABSTRACT FROM AUTHOR]

Although the appearance of Doxil alleviated the cardiotoxicity of DOX, the progression-free survival of patients was not prolonged compared with traditional medication regimens, and side effects such as hand-foot syndrome has occurred. In order to solve this dilemma, we have designed a novel co-delivery strategy to construct a co-loaded liposome of berberine (BER) and doxorubicin (DOX), which was called LipoBeDo. The optimal synergistic ratio of the two drugs was screened by cell cytotoxicity experiments in vitro , and the optimal attenuation ratio was further determined by in vivo cardiac H&E staining pathological sections. The optimal combination treatment caused a robust increase in apoptotic cells of 4T1, as compared to drug alone treatment. The prepared co-loaded liposome, LipoBeDo, had high encapsulation efficiency and good stability. The nanoliposome carrier controlled the biological fate of the drugs and maintained a pre-defined optimal ratio in vivo . The LipoBeDo significantly inhibited tumor growth in 4T1 murine mammary carcinoma model compared with Doxil ( P < 0.05), and completely overcame the myocardial rupture toxicity caused by Doxil in mice. Our co-loaded liposome delivery platform technology provided a new direction for the clinical treatment of triple-negative breast cancer and the safe application of DOX., (© 2019 Shenyang Pharmaceutical University. Published by Elsevier B.V.)

Insufficient knowledge age peculiarities of the clinical course of cardiac arrhythmias occurring asymptomatically as a manifestation of cardiotoxicity in women with breast cancer at the stage of radiation therapy, determines the high demand for research on this problem. The aim of the study was to identify and evaluate asymptomatic cardiac arrhythmias in elderly women with left breast cancer at the stage of radiation therapy. 48 women without a history of severe cardiovascular disease with HER2neu negative cancer of the left breast at the stage of 3D conformal radiotherapy were examined. Mean age 67 (64; 69). All patients at the previous stages were carried out mastectomy Madden followed by therapy with doxorubicin. The examination included ECG registration, 24-hour ECG monitoring and echocardiography. Before radiation therapy, asymptomatic arrhythmias were detected in 43 (89,6%) patients. After radiation therapy significantly increased the number of pathological supraventricular and ventricular arrhythmias as a manifestation of cardiotoxicity.

Although multiple myeloma (MM) had been an incurable hematological malignancy with a poor prognosis, recent advances in novel anti-neoplastic agents, including carfilzomib (a proteasome inhibitor), have improved the prognosis. We herein report two cases of congestive heart failure in patients treated with carfilzomib. Although there are some reports on the cardiotoxicity of carfilzomib, to our knowledge, this is the first report on the cardiac involvement of carfilzomib in Japanese MM patients. We review the critical points from our two cases, with the aim of avoiding carfilzomib-associated heart failure in MM patients.