Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse.
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.The cardiomyocytes were i...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3597611?pdf=render |
| _version_ | 1811335932034416640 |
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| author | Stefano Toldo Rachel W Goehe Marzia Lotrionte Eleonora Mezzaroma Evan T Sumner Giuseppe G L Biondi-Zoccai Ignacio M Seropian Benjamin W Van Tassell Francesco Loperfido Giovanni Palazzoni Norbert F Voelkel Antonio Abbate David A Gewirtz |
| author_facet | Stefano Toldo Rachel W Goehe Marzia Lotrionte Eleonora Mezzaroma Evan T Sumner Giuseppe G L Biondi-Zoccai Ignacio M Seropian Benjamin W Van Tassell Francesco Loperfido Giovanni Palazzoni Norbert F Voelkel Antonio Abbate David A Gewirtz |
| author_sort | Stefano Toldo |
| collection | DOAJ |
| description | 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.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.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.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. |
| first_indexed | 2024-04-13T17:31:05Z |
| format | Article |
| id | doaj.art-0039ab5e1fa44fb2948e6b8b53aba441 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T17:31:05Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0039ab5e1fa44fb2948e6b8b53aba4412022-12-22T02:37:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5842110.1371/journal.pone.0058421Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse.Stefano ToldoRachel W GoeheMarzia LotrionteEleonora MezzaromaEvan T SumnerGiuseppe G L Biondi-ZoccaiIgnacio M SeropianBenjamin W Van TassellFrancesco LoperfidoGiovanni PalazzoniNorbert F VoelkelAntonio AbbateDavid A GewirtzThe 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.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.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.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.http://europepmc.org/articles/PMC3597611?pdf=render |
| spellingShingle | Stefano Toldo Rachel W Goehe Marzia Lotrionte Eleonora Mezzaroma Evan T Sumner Giuseppe G L Biondi-Zoccai Ignacio M Seropian Benjamin W Van Tassell Francesco Loperfido Giovanni Palazzoni Norbert F Voelkel Antonio Abbate David A Gewirtz Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse. PLoS ONE |
| title | Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse. |
| title_full | Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse. |
| title_fullStr | Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse. |
| title_full_unstemmed | Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse. |
| title_short | Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse. |
| title_sort | comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse |
| url | http://europepmc.org/articles/PMC3597611?pdf=render |
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