Comparative Cardiac Toxicity of Anthracyclines In Vitro and In Vivo in the Mouse
| Autor: | Benjamin W. Van Tassell, David A. Gewirtz, Marzia Lotrionte, Giuseppe Biondi-Zoccai, Francesco Loperfido, Stefano Toldo, Giovanni Palazzoni, Norbert F. Voelkel, Ignacio M. Seropian, Antonio Abbate, Eleonora Mezzaroma, Evan T. Sumner, Rachel W. Goehe |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cardiac function curve
Male Cardiac output Anatomy and Physiology Mouse DNA damage Toxic Agents Cancer Treatment lcsh:Medicine Antineoplastic Agents Apoptosis Pharmacology Cardiovascular Toxicology Cardiovascular System Cardiovascular Pharmacology Cell Line Mice Model Organisms In vivo medicine polycyclic compounds Animals Humans Doxorubicin Anthracyclines DNA Breaks Double-Stranded Myocytes Cardiac lcsh:Science Biology Cell Proliferation Multidisciplinary Chemistry lcsh:R Heart Animal Models Oncology Echocardiography Toxicity Circulatory Physiology Medicine lcsh:Q Cardiomyopathies Reactive Oxygen Species medicine.drug Epirubicin Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 3, p e58421 (2013) |
| Popis: | Purpose The antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo. Methods The cardiomyocytes were incubated with the three anthracyclines (1 µM) to assess reactive oxygen generation, DNA damage and apoptotic cell death. CF-1 mice (10/group) received doxorubicin, epirubicin or non-pegylated liposomal-doxorubicin (10 mg/kg) and cardiac function was monitored by Doppler echocardiography to measure left ventricular ejection fraction (LVEF), heart rate (HR) and cardiac output (CO) both prior to and 10 days after drug treatment. Results In HL-1 cells, non-pegylated liposomal-doxorubicin generated significantly less reactive oxygen species (ROS), as well as less DNA damage and apoptosis activation when compared with doxorubicin and epirubicin. Cultured breast tumor cells showed similar sensitivity to the three anthracyclines. In the healthy mouse, non-pegylated liposomal doxorubicin showed a minimal and non-significant decrease in LVEF with no change in HR or CO, compared to doxorubicin and epirubicin. Conclusion This study provides evidence for reduced cardiac toxicity of non-pegylated-liposomal doxorubicin characterized by attenuation of ROS generation, DNA damage and apoptosis in comparison to epirubicin and doxorubicin. |
| Databáze: | OpenAIRE |
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