Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization-Magnetic Resonance Imaging.
Yukie MizutaTomohiko AkahoshiHinako EtoFuminori HyodoMasaharu MurataKentaro TokudaMasatoshi EtoKen YamauraPublished in: Antioxidants (Basel, Switzerland) (2022)
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.
Keyphrases
- magnetic resonance imaging
- oxidative stress
- contrast enhanced
- diabetic rats
- heart failure
- high glucose
- electron transfer
- diffusion weighted imaging
- computed tomography
- drug delivery
- endothelial cells
- atrial fibrillation
- high resolution
- cancer therapy
- magnetic resonance
- living cells
- dna damage
- drug induced
- ischemia reperfusion injury
- climate change
- signaling pathway
- metabolic syndrome
- quantum dots
- adipose tissue
- insulin resistance