TY - JOUR
T1 - Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization–Magnetic Resonance Imaging
AU - Mizuta, Yukie
AU - Akahoshi, Tomohiko
AU - Etou, Hinako
AU - Hyodo, Fuminori
AU - Murata, Masaharu
AU - Tokuda, Kentaro
AU - Eto, Masatoshi
AU - Yamaura, Ken
N1 - Funding Information:
The authors thank the Ministry of Education, Culture, Sports, Science, and Technology of Japan for providing funding.
Funding Information:
This research was funded by the Ministry of Education, Culture, Sports, Science, and Technology of Japan (JSPS KAKENHI Grant Numbers: JP21K20954 and JP22K16591). The funding body played no role in the design of the study; collection, analysis, and interpretation of data; or in writing the manuscript.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85137346882&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85137346882&partnerID=8YFLogxK
U2 - 10.3390/antiox11081454
DO - 10.3390/antiox11081454
M3 - Article
AN - SCOPUS:85137346882
SN - 2076-3921
VL - 11
JO - Antioxidants
JF - Antioxidants
IS - 8
M1 - 1454
ER -