Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20057, USA.
Radiat Res. 2012 Feb;177(2):187-99. doi: 10.1667/rr2771.1. Epub 2011 Nov 30.
Metabolomics on easily accessible biofluids has the potential to provide rapid identification and distinction between stressors and inflammatory states. In the event of a radiological event, individuals with underlying medical conditions could present with similar symptoms to radiation poisoning, prominently nausea, diarrhea, vomiting and fever. Metabolomics of radiation exposure in mice has provided valuable biomarkers, and in this study we aimed to identify biomarkers of lipopolysaccharide (LPS) exposure to compare and contrast with ionizing radiation. LPS treatment leads to a severe inflammatory response and a cytokine storm, events similar to radiation exposure, and LPS exposure can recapitulate many of the responses seen in sepsis. Urine from control mice, LPS-treated mice, and mice irradiated with 3, 8 and 15 Gy of γ rays was analyzed by LCMS, and markers were extracted using SIMCA-P(+) and Random Forests. Markers were validated through tandem mass spectrometry against pure chemicals. Five metabolites, cytosine, cortisol, adenine, O-propanoylcarnitine and isethionic acid, showed increased excretion at 24 h after LPS treatment (P < 0.0001, 0.0393, 0.0393, <0.0001 and 0.0004, respectively). Of these, cytosine, adenine and O-propanoylcarnitine showed specificity to LPS treatment when compared to radiation. On the other hand, increased excretion of cortisol after LPS and radiation treatments indicated a rapid systemic response to inflammatory agents. Isethionic acid excretion, however, showed elevated levels not only after LPS treatment but also after a very high dose of radiation (15 Gy), while additional metabolites showed responsiveness to radiation but not LPS. Metabolomics therefore has the potential to distinguish between different inflammatory responses based on differential ion signatures. It can also provide quick and reliable assessment of medical conditions in a mass casualty radiological scenario and aid in effective triaging.
代谢组学分析易于获得的生物体液具有快速识别和区分应激源和炎症状态的潜力。在发生放射性事件的情况下，患有潜在疾病的个体可能会出现类似于辐射中毒的症状，主要有恶心、腹泻、呕吐和发烧。对小鼠辐射暴露的代谢组学研究提供了有价值的生物标志物，本研究旨在确定脂多糖 (LPS) 暴露的生物标志物，以便与电离辐射进行比较和对照。LPS 处理会导致严重的炎症反应和细胞因子风暴，这些事件类似于辐射暴露，而 LPS 暴露可以再现许多脓毒症中观察到的反应。用 LCMS 分析来自对照小鼠、LPS 处理小鼠和接受 3、8 和 15 Gy γ 射线照射的小鼠的尿液，使用 SIMCA-P(+) 和随机森林提取标记物。通过串联质谱法对纯化学物质验证标记物。在 LPS 处理后 24 小时，五种代谢物（胞嘧啶、皮质醇、腺嘌呤、O-丙酰肉碱和异硫氨酸）的排泄量增加（P < 0.0001、0.0393、0.0393、<0.0001 和 0.0004，分别）。其中，与辐射相比，胞嘧啶、腺嘌呤和 O-丙酰肉碱的特异性最强。另一方面，皮质醇在 LPS 和辐射处理后的排泄增加表明对炎症剂的快速全身反应。然而，异硫氨酸的排泄不仅在 LPS 处理后升高，而且在非常高的剂量（15 Gy）后也升高，而其他代谢物对辐射有反应，但对 LPS 没有反应。因此，代谢组学有可能根据不同的离子特征区分不同的炎症反应。它还可以快速可靠地评估大规模放射性伤亡场景中的医疗状况，并有助于进行有效的分诊。
