Imaging of Hydroxyl-Radical Generation Using Dynamic Nuclear Polarization-Magnetic Resonance Imaging and a Spin-Trapping Agent
Imaging of Hydroxyl-Radical Generation Using Dynamic Nuclear Polarization-Magnetic Resonance Imaging and a Spin-Trapping Agent
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DOI：
10.1021/acs.analchem.0c02331
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发表时间：
2020-11-03
影响因子：
7.4
通讯作者：
Matsuo, Masayuki
中科院分区：
文献类型：
--
作者：
Shoda, Shinichi;Hyodo, Fuminori;Matsuo, Masayuki
活性氧(ROS)在细胞代谢中起着重要的作用，但它们也会对生物分子造成氧化损伤。在ROS中，羟基自由基因其较高的反应速率常数而成为生物体系中活性最强的分子之一。因此，中心点OH的成像可用于氧化还原机制的评估和氧化性疾病的诊断。体内动态核极化磁共振成像(DNP-MRI)是一种在MRI解剖分辨率下获得自由基时空信息的无创性成像方法。在这项研究中，我们通过将DNP-MRI与中心点OH的自旋捕捉剂(DMPO：5，5-二甲基-1-吡咯啉N-氧化物)相结合来研究Fenton反应产生的羟基自由基的可视化。此外，我们还通过DNP-MRI验证了四种硫醇相关试剂对自由基的清除作用。我们首次用DNP-MRI/自旋捕捉方法和可视化中心点OH产生的方法证明了DMPO-OH自由基可以诱导DNP的增强。在474.5兆赫的电子顺磁共振辐照频率下，观察到最大的dnp增强。同时，通过DMPO-OH的DNP图像值的降低来评价其清除自由基的效果。我们方法的一个优点是可以同时研究化合物的活性和清除自由基的作用。
Reactive oxygen species (ROS) play an important role in cell metabolism, but they can cause oxidative damage to biomolecules. Among ROS, the hydroxyl radical (center dot OH) is one of the most reactive molecules in biological systems because of its high reaction rate constant. Therefore, imaging of center dot OH could be useful for evaluation of the redox mechanism and diagnosis of oxidative diseases. In vivo dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) is a noninvasive imaging method to obtain spatiotemporal information about free radicals with MRI anatomical resolution. In this study, we investigated the visualization of hydroxyl radicals generated from the Fenton reaction by combining DNP-MRI with a spin-trapping agent (DMPO: 5,5-dimethyl-1-pyrroline N-oxide) for center dot OH. Additionally, we demonstrated the radical-scavenging effect using four thiol-related reagents by DNP-MRI. We demonstrated that DNP enhancement could be induced by the DMPO-OH radical using the DNP-MRI/spin-trapping method and visualized center dot OH generation for the first time. Maximum DNP enhancement was observed at an electron paramagnetic resonance irradiation frequency of 474.5 MHz. Furthermore, the radical-scavenging effect was simultaneously evaluated by the decrease in the DNP image value of DMPO-OH. An advantage of our methods is that they simultaneously investigate compound activity and the radical-scavenging effect.