Folic acid reduces doxorubicin-induced cardiomyopathy by modulating endothelial nitric oxide synthase

Yanti Octavia; Georgios Kararigas; Martine de Boer; Ihsan Chrifi; Rinrada Kietadisorn; Melissa Swinnen; Hans Duimel; Fons K. Verheyen; Maarten M. Brandt; Daniela Fliegner; Caroline Cheng; Stefan Janssens; Dirk J. Duncker; An L. Moens

doi:10.1111/jcmm.13231

Folic acid reduces doxorubicin-induced cardiomyopathy by modulating endothelial nitric oxide synthase

Yanti Octavia, Georgios Kararigas^*, Martine de Boer, Ihsan Chrifi, Rinrada Kietadisorn, Melissa Swinnen, Hans Duimel, Fons K. Verheyen, Maarten M. Brandt, Daniela Fliegner, Caroline Cheng, Stefan Janssens, Dirk J. Duncker^*, An L. Moens

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The use of doxorubicin (DOXO) as a chemotherapeutic drug has been hampered by cardiotoxicity leading to cardiomyopathy and heart failure. Folic acid (FA) is a modulator of endothelial nitric oxide (NO) synthase (eNOS), which in turn is an important player in diseases associated with NO insufficiency or NOS dysregulation, such as pressure overload and myocardial infarction. However, the role of FA in DOXO-induced cardiomyopathy is poorly understood. The aim of this study was to test the hypothesis that FA prevents DOXO-induced cardiomyopathy by modulating eNOS and mitochondrial structure and function. Male C57BL/6 mice were randomized to a single dose of DOXO (20mg/kg intraperitoneal) or sham. FA supplementation (10mg/day per oral) was started 7days before DOXO injection and continued thereafter. DOXO resulted in 70% mortality after 10days, with the surviving mice demonstrating a 30% reduction in stroke volume compared with sham groups. Pre-treatment with FA reduced mortality to 45% and improved stroke volume (both P

Original language	English
Pages (from-to)	3277-3287
Number of pages	11
Journal	Journal of Cellular and Molecular Medicine
Volume	21
Issue number	12
DOIs	https://doi.org/10.1111/jcmm.13231
Publication status	Published - Dec 2017

Keywords

anthracycline
antioxidant enzyme
cardiotoxicity
free radical
nitric oxide
LEFT-VENTRICULAR DYSFUNCTION
CARDIAC DYSFUNCTION
CARDIOVASCULAR-DISEASE
INDUCED CARDIOTOXICITY
MITOCHONDRIAL-FUNCTION
PRESSURE-OVERLOAD
HEART-FAILURE
MORTALITY
PROTECTS
INJURY

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Cite this

Octavia, Y., Kararigas, G., de Boer, M., Chrifi, I., Kietadisorn, R., Swinnen, M., Duimel, H., Verheyen, F. K., Brandt, M. M., Fliegner, D., Cheng, C., Janssens, S., Duncker, D. J., & Moens, A. L. (2017). Folic acid reduces doxorubicin-induced cardiomyopathy by modulating endothelial nitric oxide synthase. Journal of Cellular and Molecular Medicine, 21(12), 3277-3287. https://doi.org/10.1111/jcmm.13231

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title = "Folic acid reduces doxorubicin-induced cardiomyopathy by modulating endothelial nitric oxide synthase",

abstract = "The use of doxorubicin (DOXO) as a chemotherapeutic drug has been hampered by cardiotoxicity leading to cardiomyopathy and heart failure. Folic acid (FA) is a modulator of endothelial nitric oxide (NO) synthase (eNOS), which in turn is an important player in diseases associated with NO insufficiency or NOS dysregulation, such as pressure overload and myocardial infarction. However, the role of FA in DOXO-induced cardiomyopathy is poorly understood. The aim of this study was to test the hypothesis that FA prevents DOXO-induced cardiomyopathy by modulating eNOS and mitochondrial structure and function. Male C57BL/6 mice were randomized to a single dose of DOXO (20mg/kg intraperitoneal) or sham. FA supplementation (10mg/day per oral) was started 7days before DOXO injection and continued thereafter. DOXO resulted in 70% mortality after 10days, with the surviving mice demonstrating a 30% reduction in stroke volume compared with sham groups. Pre-treatment with FA reduced mortality to 45% and improved stroke volume (both P",

keywords = "anthracycline, antioxidant enzyme, cardiotoxicity, free radical, nitric oxide, LEFT-VENTRICULAR DYSFUNCTION, CARDIAC DYSFUNCTION, CARDIOVASCULAR-DISEASE, INDUCED CARDIOTOXICITY, MITOCHONDRIAL-FUNCTION, PRESSURE-OVERLOAD, HEART-FAILURE, MORTALITY, PROTECTS, INJURY",

author = "Yanti Octavia and Georgios Kararigas and {de Boer}, Martine and Ihsan Chrifi and Rinrada Kietadisorn and Melissa Swinnen and Hans Duimel and Verheyen, {Fons K.} and Brandt, {Maarten M.} and Daniela Fliegner and Caroline Cheng and Stefan Janssens and Duncker, {Dirk J.} and Moens, {An L.}",

year = "2017",

month = dec,

doi = "10.1111/jcmm.13231",

language = "English",

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pages = "3277--3287",

journal = "Journal of Cellular and Molecular Medicine",

issn = "1582-1838",

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Octavia, Y, Kararigas, G, de Boer, M, Chrifi, I, Kietadisorn, R, Swinnen, M, Duimel, H, Verheyen, FK, Brandt, MM, Fliegner, D, Cheng, C, Janssens, S, Duncker, DJ & Moens, AL 2017, 'Folic acid reduces doxorubicin-induced cardiomyopathy by modulating endothelial nitric oxide synthase', Journal of Cellular and Molecular Medicine, vol. 21, no. 12, pp. 3277-3287. https://doi.org/10.1111/jcmm.13231

TY - JOUR

T1 - Folic acid reduces doxorubicin-induced cardiomyopathy by modulating endothelial nitric oxide synthase

AU - Octavia, Yanti

AU - Kararigas, Georgios

AU - de Boer, Martine

AU - Chrifi, Ihsan

AU - Kietadisorn, Rinrada

AU - Swinnen, Melissa

AU - Duimel, Hans

AU - Verheyen, Fons K.

AU - Brandt, Maarten M.

AU - Fliegner, Daniela

AU - Cheng, Caroline

AU - Janssens, Stefan

AU - Duncker, Dirk J.

AU - Moens, An L.

PY - 2017/12

Y1 - 2017/12

N2 - The use of doxorubicin (DOXO) as a chemotherapeutic drug has been hampered by cardiotoxicity leading to cardiomyopathy and heart failure. Folic acid (FA) is a modulator of endothelial nitric oxide (NO) synthase (eNOS), which in turn is an important player in diseases associated with NO insufficiency or NOS dysregulation, such as pressure overload and myocardial infarction. However, the role of FA in DOXO-induced cardiomyopathy is poorly understood. The aim of this study was to test the hypothesis that FA prevents DOXO-induced cardiomyopathy by modulating eNOS and mitochondrial structure and function. Male C57BL/6 mice were randomized to a single dose of DOXO (20mg/kg intraperitoneal) or sham. FA supplementation (10mg/day per oral) was started 7days before DOXO injection and continued thereafter. DOXO resulted in 70% mortality after 10days, with the surviving mice demonstrating a 30% reduction in stroke volume compared with sham groups. Pre-treatment with FA reduced mortality to 45% and improved stroke volume (both P

AB - The use of doxorubicin (DOXO) as a chemotherapeutic drug has been hampered by cardiotoxicity leading to cardiomyopathy and heart failure. Folic acid (FA) is a modulator of endothelial nitric oxide (NO) synthase (eNOS), which in turn is an important player in diseases associated with NO insufficiency or NOS dysregulation, such as pressure overload and myocardial infarction. However, the role of FA in DOXO-induced cardiomyopathy is poorly understood. The aim of this study was to test the hypothesis that FA prevents DOXO-induced cardiomyopathy by modulating eNOS and mitochondrial structure and function. Male C57BL/6 mice were randomized to a single dose of DOXO (20mg/kg intraperitoneal) or sham. FA supplementation (10mg/day per oral) was started 7days before DOXO injection and continued thereafter. DOXO resulted in 70% mortality after 10days, with the surviving mice demonstrating a 30% reduction in stroke volume compared with sham groups. Pre-treatment with FA reduced mortality to 45% and improved stroke volume (both P

KW - anthracycline

KW - antioxidant enzyme

KW - cardiotoxicity

KW - free radical

KW - nitric oxide

KW - LEFT-VENTRICULAR DYSFUNCTION

KW - CARDIAC DYSFUNCTION

KW - CARDIOVASCULAR-DISEASE

KW - INDUCED CARDIOTOXICITY

KW - MITOCHONDRIAL-FUNCTION

KW - PRESSURE-OVERLOAD

KW - HEART-FAILURE

KW - MORTALITY

KW - PROTECTS

KW - INJURY

U2 - 10.1111/jcmm.13231

DO - 10.1111/jcmm.13231

M3 - Article

SN - 1582-1838

VL - 21

SP - 3277

EP - 3287

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

IS - 12

ER -