Exposure to ionizing radiation following a nuclear or radiological incident results in potential acute radiation syndromes causing sequelae of multi-organ injury in a dose- and time-dependent manner. Currently, medical countermeasures against radiation injury are limited, and no biomarkers have been approved by regulatory authorities. Identification of circulating plasma biomarkers indicative of radiation injury can be useful for early triage and injury assessment and in the development of novel therapies (medical countermeasures). Aims of this study are to (1) identify metabolites and lipids with consensus signatures that can inform on mechanism of injury in radiation-induced multi-organ injury and (2) identify plasma biomarkers in non-human primate (NHP) that correlate with tissues (kidney, liver, lung, left and right heart, jejunum) indicative of radiation injury, assessing samples collected over 3 wk post-exposure to 12 Gy partial body irradiation with 2.5% bone marrow sparing. About 180 plasma and tissue metabolites and lipids were quantified through Biocrates AbsoluteIDQ p180 kit using liquid chromatography and mass spectrometry. System-wide perturbations of specific metabolites and lipid levels and pathway alterations were identified. Citrulline, Serotonin, PC ae 38:2, PC ae 36:2, and sum of branched chain amino acids were identified as potential biomarkers of radiation injury. Pathway analysis revealed consistent changes in fatty acid oxidation and metabolism and perturbations in multiple other pathways.

中文翻译：

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非人类灵长类动物模型中多器官辐射损伤的代谢组学揭示了全系统代谢扰动。

核或放射性事件后暴露于电离辐射会导致潜在的急性辐射综合征，从而以剂量和时间依赖性方式引起多器官损伤的后遗症。目前，针对辐射损伤的医学对策有限，也没有任何生物标志物获得监管机构批准。识别指示辐射损伤的循环血浆生物标志物可用于早期分类和损伤评估以及新疗法（医疗对策）的开发。本研究的目的是 (1) 识别具有共识特征的代谢物和脂质，这些特征可以了解辐射引起的多器官损伤的损伤机制；(2) 识别非人类灵长类动物 (NHP) 中与组织相关的血浆生物标志物（肾、肝、肺、左心、右心、空肠）指示放射损伤，评估暴露于 12 Gy 局部身体照射后 3 周内收集的样本，保留 2.5% 骨髓。通过 Biocrates AbsoluteIDQ p180 试剂盒使用液相色谱和质谱法对约 180 种血浆和组织代谢物和脂质进行了定量。确定了特定代谢物和脂质水平的全系统扰动以及途径改变。瓜氨酸、血清素、PC ae 38:2、PC ae 36:2 和支链氨基酸总和被确定为辐射损伤的潜在生物标志物。通路分析揭示了脂肪酸氧化和代谢的一致变化以及多个其他通路的扰动。