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Comparing Flaxseed and Perindopril in the Prevention of Doxorubicin and Trastuzumab-Induced Cardiotoxicity in C57Bl/6 Mice

Background: Two anti-cancer agents, doxorubicin (DOX) and trastuzumab (TRZ), are commonly used in the management of breast cancer in women. Despite their efficacy in reducing the morbidity and mortality of individuals with breast cancer, the use of these agents is limited by adverse cardiotoxic side...

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Autores principales: Eekhoudt, Cameron R., Bortoluzzi, Tessa, Varghese, Sonu S., Cheung, David Y. C., Christie, Simon, Eastman, Skyler, Mittal, Ishika, Austria, J. Alejandro, Aukema, Harold M., Ravandi, Amir, Thliveris, James, Singal, Pawan K., Jassal, Davinder S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139942/
https://www.ncbi.nlm.nih.gov/pubmed/35621631
http://dx.doi.org/10.3390/curroncol29050241
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author Eekhoudt, Cameron R.
Bortoluzzi, Tessa
Varghese, Sonu S.
Cheung, David Y. C.
Christie, Simon
Eastman, Skyler
Mittal, Ishika
Austria, J. Alejandro
Aukema, Harold M.
Ravandi, Amir
Thliveris, James
Singal, Pawan K.
Jassal, Davinder S.
author_facet Eekhoudt, Cameron R.
Bortoluzzi, Tessa
Varghese, Sonu S.
Cheung, David Y. C.
Christie, Simon
Eastman, Skyler
Mittal, Ishika
Austria, J. Alejandro
Aukema, Harold M.
Ravandi, Amir
Thliveris, James
Singal, Pawan K.
Jassal, Davinder S.
author_sort Eekhoudt, Cameron R.
collection PubMed
description Background: Two anti-cancer agents, doxorubicin (DOX) and trastuzumab (TRZ), are commonly used in the management of breast cancer in women. Despite their efficacy in reducing the morbidity and mortality of individuals with breast cancer, the use of these agents is limited by adverse cardiotoxic side effects. Both the nutraceutical agent flaxseed (FLX) and the pharmaceutical drug perindopril (PER) have been studied individually in the prevention of chemotherapy-mediated cardiac dysfunction. The objective of this study was to determine whether the prophylactic administration of FLX is comparable and/or synergistic with PER in preventing DOX + TRZ-induced cardiotoxicity. Methods: Over a six-week period, 81 wild-type C57Bl/6 female mice (8–12 weeks old) were randomized to receive regular chow (RC) or 10% FLX-supplemented diets with or without PER (3 mg/kg/week; oral gavage). Starting at week 4, mice were randomized to receive a weekly injection of saline or DOX (8 mg/kg) + TRZ (3 mg/kg). Serial echocardiography was conducted weekly and histological and biochemical analyses were performed at the end of the study. Results: In mice treated with RC + DOX + TRZ, left ventricular ejection (LVEF) decreased from 75 ± 2% at baseline to 37 ± 3% at week 6. However, prophylactic treatment with either FLX, PER, or FLX + PER partially preserved left ventricular systolic function with LVEF values of 61 ± 2%, 62 ± 2%, and 64 ± 2%, respectively. The administration of FLX, PER, or FLX + PER was also partially cardioprotective in preserving cardiomyocyte integrity and attenuating the expression of the inflammatory biomarker NF-κB due to DOX + TRZ administration. Conclusion: FLX was equivalent to PER at preventing DOX + TRZ-induced cardiotoxicity in a chronic in vivo murine model.
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spelling pubmed-91399422022-05-28 Comparing Flaxseed and Perindopril in the Prevention of Doxorubicin and Trastuzumab-Induced Cardiotoxicity in C57Bl/6 Mice Eekhoudt, Cameron R. Bortoluzzi, Tessa Varghese, Sonu S. Cheung, David Y. C. Christie, Simon Eastman, Skyler Mittal, Ishika Austria, J. Alejandro Aukema, Harold M. Ravandi, Amir Thliveris, James Singal, Pawan K. Jassal, Davinder S. Curr Oncol Article Background: Two anti-cancer agents, doxorubicin (DOX) and trastuzumab (TRZ), are commonly used in the management of breast cancer in women. Despite their efficacy in reducing the morbidity and mortality of individuals with breast cancer, the use of these agents is limited by adverse cardiotoxic side effects. Both the nutraceutical agent flaxseed (FLX) and the pharmaceutical drug perindopril (PER) have been studied individually in the prevention of chemotherapy-mediated cardiac dysfunction. The objective of this study was to determine whether the prophylactic administration of FLX is comparable and/or synergistic with PER in preventing DOX + TRZ-induced cardiotoxicity. Methods: Over a six-week period, 81 wild-type C57Bl/6 female mice (8–12 weeks old) were randomized to receive regular chow (RC) or 10% FLX-supplemented diets with or without PER (3 mg/kg/week; oral gavage). Starting at week 4, mice were randomized to receive a weekly injection of saline or DOX (8 mg/kg) + TRZ (3 mg/kg). Serial echocardiography was conducted weekly and histological and biochemical analyses were performed at the end of the study. Results: In mice treated with RC + DOX + TRZ, left ventricular ejection (LVEF) decreased from 75 ± 2% at baseline to 37 ± 3% at week 6. However, prophylactic treatment with either FLX, PER, or FLX + PER partially preserved left ventricular systolic function with LVEF values of 61 ± 2%, 62 ± 2%, and 64 ± 2%, respectively. The administration of FLX, PER, or FLX + PER was also partially cardioprotective in preserving cardiomyocyte integrity and attenuating the expression of the inflammatory biomarker NF-κB due to DOX + TRZ administration. Conclusion: FLX was equivalent to PER at preventing DOX + TRZ-induced cardiotoxicity in a chronic in vivo murine model. MDPI 2022-04-21 /pmc/articles/PMC9139942/ /pubmed/35621631 http://dx.doi.org/10.3390/curroncol29050241 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Eekhoudt, Cameron R.
Bortoluzzi, Tessa
Varghese, Sonu S.
Cheung, David Y. C.
Christie, Simon
Eastman, Skyler
Mittal, Ishika
Austria, J. Alejandro
Aukema, Harold M.
Ravandi, Amir
Thliveris, James
Singal, Pawan K.
Jassal, Davinder S.
Comparing Flaxseed and Perindopril in the Prevention of Doxorubicin and Trastuzumab-Induced Cardiotoxicity in C57Bl/6 Mice
title Comparing Flaxseed and Perindopril in the Prevention of Doxorubicin and Trastuzumab-Induced Cardiotoxicity in C57Bl/6 Mice
title_full Comparing Flaxseed and Perindopril in the Prevention of Doxorubicin and Trastuzumab-Induced Cardiotoxicity in C57Bl/6 Mice
title_fullStr Comparing Flaxseed and Perindopril in the Prevention of Doxorubicin and Trastuzumab-Induced Cardiotoxicity in C57Bl/6 Mice
title_full_unstemmed Comparing Flaxseed and Perindopril in the Prevention of Doxorubicin and Trastuzumab-Induced Cardiotoxicity in C57Bl/6 Mice
title_short Comparing Flaxseed and Perindopril in the Prevention of Doxorubicin and Trastuzumab-Induced Cardiotoxicity in C57Bl/6 Mice
title_sort comparing flaxseed and perindopril in the prevention of doxorubicin and trastuzumab-induced cardiotoxicity in c57bl/6 mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139942/
https://www.ncbi.nlm.nih.gov/pubmed/35621631
http://dx.doi.org/10.3390/curroncol29050241
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