Effects of oxygen challenging to tissue redox and pO2 status.
Effects of oxygen challenging to tissue redox and pO2 status.
复制标题
氧气对组织氧化还原和 pO2 状态的影响。
DOI：
10.1016/j.freeradbiomed.2018.10.454
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发表时间：
2019
影响因子：
7.4
通讯作者：
Krishna,MuraliC
中科院分区：
文献类型：
--
作者：
Matsumoto,Ken-Ichiro;Mitchell,JamesB;Krishna,MuraliC
氮氧化物自由基可以作为氧化还原敏感的MRI造影剂，用于成像感兴趣的组织的氧化还原状态。本研究评估了吸入气体中氧含量对小鼠肌肉和肿瘤中三种氮氧化物代谢动力学的影响。制备雌性C3H/Hen mtv小鼠右后腿SCC肿瘤，大小约1.0 cm3。采用磁共振氧化还原成像技术，比较了3-羧基-2,2,5,5-四甲基吡咯烷- n -氧（CxP）、3-氨基甲酰-2,2,5,5-四甲基吡咯烷- n -氧（CmP）和4-羟基-四甲基哌啶- n -氧（TEMPOL）三种具有不同亲脂性的硝基氧化物。利用多层多回波（MSME）序列与多个TRs获得组织的t1映射。三种氮氧化物在肌肉和肿瘤中的积累和代谢/清除表现出差异。细胞不透性氮氧化物CxP表现出缓慢增强然后缓慢下降的动力学模式，典型的清除而不是代谢。另一方面，细胞渗透性CmP在肿瘤中表现出相对较快的摄取和代谢，代谢率略高于肌肉。TEMPOL在肿瘤组织中呈快速吸收和降低的趋势，且衰减速率明显加快，而在正常肌肉中最大信号强度略高，衰减速率较慢。当呼吸气体为100%氧气时，肿瘤中TEMPOL的降低率显著提高，而在肌肉中则无显著差异。监测TEMPOL氧依赖线宽的EPR血氧仪研究表明，与空气呼吸相比，碳呼吸时健康组织中的po2显著增加正常组织的po2，而100%氧气呼吸使正常组织轻度缺氧。由于TEMPOL是一种辐射防护剂，我们的研究表明，100%氧气呼吸和TEMPOL的结合有可能增强对正常组织的辐射防护作用。
Nitroxide free radicals can serve as redox-sensitive MRI contrast agents useful to image the redox status of tissue of interest. In this study, the effect of oxygen content in the inspired gas on the kinetics of metabolism of three nitroxides has been evaluated in the muscle and tumor in mice.SCC tumors (approximate size of 1.0 cm3) on the right hind leg of female C3H/Hen MTV-mice were prepared. Three nitroxides, 3-carboxy-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CxP), 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP), and 4-hydroxy-tetramethylpiperidine-N-oxyl (TEMPOL), having different lipophilicities were compared using MR redox imaging. T1-mapping of the tissues was obtained using a multi-slice multi-echo (MSME) sequence with several TRs.The three nitroxides showed differences in accumulation and metabolism/clearance in muscle and tumor. The cell impermeable nitroxide CxP displayed kinetic patterns of slow enhancement followed by a slow decline typical of clearance rather than metabolism. The cell permeable CmP on the other hand showed a relatively faster uptake and metabolism with a modestly higher rate of metabolism in the tumor than muscle. The TEMPOL on the other hand displayed a rapid uptake and reduction with a trend of significantly rapid decay rate in tumor tissue, while slightly higher maximum signal intensity and slower decay rate was observed in normal muscle. The reduction rate of TEMPOL in the tumor was significantly enhanced when the breathing gas had 100%-oxygen while it was not significantly different in the muscle. EPR oximetry studies monitoring the oxygen dependent linewidth of TEMPOL showed that the pO2in the healthy tissue during carbogen breathing significantly increased normal tissue pO2compared to air breathing whereas breathing 100%-oxygen made normal tissue slight hypoxic. Since TEMPOL is a radioprotector, our studies show that a combination of 100%-oxygen breathing and TEMPOL has a potential to enhance radioprotective effects to normal tissue.