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Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization–Magnetic Resonance Imaging

Doxorubicin (DOX) induces dose-dependent cardiotoxicity via oxidative stress and abnormal mitochondrial function in the myocardium. Therefore, a noninvasive in vivo imaging procedure for monitoring the redox status of the heart may aid in monitoring diseases and developing treatments. However, an ap...

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Autores principales: Mizuta, Yukie, Akahoshi, Tomohiko, Eto, Hinako, Hyodo, Fuminori, Murata, Masaharu, Tokuda, Kentaro, Eto, Masatoshi, Yamaura, Ken
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331045/
https://www.ncbi.nlm.nih.gov/pubmed/35892655
http://dx.doi.org/10.3390/antiox11081454
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author Mizuta, Yukie
Akahoshi, Tomohiko
Eto, Hinako
Hyodo, Fuminori
Murata, Masaharu
Tokuda, Kentaro
Eto, Masatoshi
Yamaura, Ken
author_facet Mizuta, Yukie
Akahoshi, Tomohiko
Eto, Hinako
Hyodo, Fuminori
Murata, Masaharu
Tokuda, Kentaro
Eto, Masatoshi
Yamaura, Ken
author_sort Mizuta, Yukie
collection PubMed
description Doxorubicin (DOX) induces dose-dependent cardiotoxicity via oxidative stress and abnormal mitochondrial function in the myocardium. Therefore, a noninvasive in vivo imaging procedure for monitoring the redox status of the heart may aid in monitoring diseases and developing treatments. However, an appropriate technique has yet to be developed. In this study, we demonstrate a technique for detecting and visualizing the redox status of the heart using in vivo dynamic nuclear polarization–magnetic resonance imaging (DNP–MRI) with 3-carbamoyl-PROXYL (CmP) as a molecular imaging probe. Male C57BL/6N mice were administered DOX (20 mg/kg) or saline. DNP–MRI clearly showed a slower DNP signal reduction in the DOX group than in the control group. Importantly, the difference in the DNP signal reduction rate between the two groups occurred earlier than that detected by physiological examination or clinical symptoms. In an in vitro experiment, KCN (an inhibitor of complex IV in the mitochondrial electron transport chain) and DOX inhibited the electron paramagnetic resonance change in H9c2 cardiomyocytes, suggesting that the redox metabolism of CmP in the myocardium is mitochondrion-dependent. Therefore, this molecular imaging technique has the potential to monitor the dynamics of redox metabolic changes in DOX-induced cardiomyopathy and facilitate an early diagnosis of this condition.
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spelling pubmed-93310452022-07-29 Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization–Magnetic Resonance Imaging Mizuta, Yukie Akahoshi, Tomohiko Eto, Hinako Hyodo, Fuminori Murata, Masaharu Tokuda, Kentaro Eto, Masatoshi Yamaura, Ken Antioxidants (Basel) Article Doxorubicin (DOX) induces dose-dependent cardiotoxicity via oxidative stress and abnormal mitochondrial function in the myocardium. Therefore, a noninvasive in vivo imaging procedure for monitoring the redox status of the heart may aid in monitoring diseases and developing treatments. However, an appropriate technique has yet to be developed. In this study, we demonstrate a technique for detecting and visualizing the redox status of the heart using in vivo dynamic nuclear polarization–magnetic resonance imaging (DNP–MRI) with 3-carbamoyl-PROXYL (CmP) as a molecular imaging probe. Male C57BL/6N mice were administered DOX (20 mg/kg) or saline. DNP–MRI clearly showed a slower DNP signal reduction in the DOX group than in the control group. Importantly, the difference in the DNP signal reduction rate between the two groups occurred earlier than that detected by physiological examination or clinical symptoms. In an in vitro experiment, KCN (an inhibitor of complex IV in the mitochondrial electron transport chain) and DOX inhibited the electron paramagnetic resonance change in H9c2 cardiomyocytes, suggesting that the redox metabolism of CmP in the myocardium is mitochondrion-dependent. Therefore, this molecular imaging technique has the potential to monitor the dynamics of redox metabolic changes in DOX-induced cardiomyopathy and facilitate an early diagnosis of this condition. MDPI 2022-07-26 /pmc/articles/PMC9331045/ /pubmed/35892655 http://dx.doi.org/10.3390/antiox11081454 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
Mizuta, Yukie
Akahoshi, Tomohiko
Eto, Hinako
Hyodo, Fuminori
Murata, Masaharu
Tokuda, Kentaro
Eto, Masatoshi
Yamaura, Ken
Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization–Magnetic Resonance Imaging
title Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization–Magnetic Resonance Imaging
title_full Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization–Magnetic Resonance Imaging
title_fullStr Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization–Magnetic Resonance Imaging
title_full_unstemmed Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization–Magnetic Resonance Imaging
title_short Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization–Magnetic Resonance Imaging
title_sort noninvasive diagnosis of the mitochondrial function of doxorubicin-induced cardiomyopathy using in vivo dynamic nuclear polarization–magnetic resonance imaging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331045/
https://www.ncbi.nlm.nih.gov/pubmed/35892655
http://dx.doi.org/10.3390/antiox11081454
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