Vicente Elisabeth, Vujaskovic Zeljko, Jackson Isabel L
Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Metabolites. 2020 Jun 20;10(6):259. doi: 10.3390/metabo10060259.
A large-scale nuclear event has the ability to inflict mass casualties requiring point-of-care and laboratory-based diagnostic and prognostic biomarkers to inform victim triage and appropriate medical intervention. Extensive progress has been made to develop post-exposure point-of-care biodosimetry assays and to identify biomarkers that may be used in early phase testing to predict the course of the disease. Screening for biomarkers has recently extended to identify specific metabolomic and lipidomic responses to radiation using animal models. The objective of this review was to determine which metabolites or lipids most frequently experienced perturbations post-ionizing irradiation (IR) in preclinical studies using animal models of acute radiation sickness (ARS) and delayed effects of acute radiation exposure (DEARE). Upon review of approximately 65 manuscripts published in the peer-reviewed literature, the most frequently referenced metabolites showing clear changes in IR induced injury were found to be citrulline, citric acid, creatine, taurine, carnitine, xanthine, creatinine, hypoxanthine, uric acid, and threonine. Each metabolite was evaluated by specific study parameters to determine whether trends were in agreement across several studies. A select few show agreement across variable animal models, IR doses and timepoints, indicating that they may be ubiquitous and appropriate for use in diagnostic or prognostic biomarker panels.
大规模核事件有能力造成大量人员伤亡，这就需要即时护理和基于实验室的诊断及预后生物标志物，以便为受害者分诊和适当的医疗干预提供依据。在开发暴露后即时护理生物剂量测定法以及识别可用于早期检测以预测疾病进程的生物标志物方面已取得了广泛进展。最近，生物标志物的筛选已扩展到使用动物模型来识别对辐射的特定代谢组学和脂质组学反应。本综述的目的是确定在使用急性放射病（ARS）和急性辐射暴露延迟效应（DEARE）动物模型的临床前研究中，哪些代谢物或脂质在电离辐射（IR）后最常出现扰动。在查阅了同行评审文献中发表的约65篇手稿后，发现最常被引用的在IR诱导损伤中显示出明显变化的代谢物是瓜氨酸、柠檬酸、肌酸、牛磺酸、肉碱、黄嘌呤、肌酐、次黄嘌呤、尿酸和苏氨酸。通过特定的研究参数对每种代谢物进行评估，以确定不同研究中的趋势是否一致。少数几种在不同的动物模型、IR剂量和时间点上表现出一致性，表明它们可能普遍存在且适用于诊断或预后生物标志物组合。
