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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9331045 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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