Radiation exposure induces cross-species temporal metabolic changes that are mitigated in mice by amifostine.
Radiation exposure induces cross-species temporal metabolic changes that are mitigated in mice by amifostine.
复制标题
辐射暴露诱导跨物种的时间代谢变化，在小鼠中通过氨磷汀减轻。
DOI：
10.1038/s41598-021-93401-7
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发表时间：
2021-07-07
影响因子：
4.6
通讯作者：
Powers R
中科院分区：
文献类型：
--
作者：
Crook A;De Lima Leite A;Payne T;Bhinderwala F;Woods J;Singh VK;Powers R
从癌症治疗和工业事故到恐怖袭击和军事行动等各种事件都可能发生暴露于急性、破坏性辐射的情况。我们对如何保护个人并减轻辐射损伤或急性辐射综合症（ARS）影响的理解仍然有限。美国食品和药物管理局批准的 ARS 疗法仅有少数几种；而氨磷汀仅限于治疗癌症放射治疗引起的低剂量（0.7-6 Gy）辐射中毒。早期干预对于治疗 ARS 至关重要，这需要识别诊断生物标志物来快速表征辐射暴露。为此，进行了一项多平台代谢组学研究，以全面表征 γ 辐射后小鼠和非人灵长类动物血清样本代谢物水平的时间变化。氨磷汀的代谢组学特征也在小鼠中作为辐射防护模型进行了评估。核磁共振和质谱代谢组学分析确定了 23 条因辐射暴露而失调的途径。这些代谢组学的改变在葡萄糖代谢、磷脂生物合成和核苷酸代谢中表现出不同的轨迹。通过氨磷汀治疗，这些途径在辐射暴露一周内恢复到基线水平。总之，我们的数据表明了一种独特的生理变化，该变化与辐射剂量或物种无关。此外，通过使用氨磷汀预防 ARS 观察到辐射防护的代谢特征。
Exposure to acute, damaging radiation may occur through a variety of events from cancer therapy and industrial accidents to terrorist attacks and military actions. Our understanding of how to protect individuals and mitigate the effects of radiation injury or Acute Radiation Syndrome (ARS) is still limited. There are only a few Food and Drug Administration-approved therapies for ARS; whereas, amifostine is limited to treating low dose (0.7–6 Gy) radiation poisoning arising from cancer radiotherapy. An early intervention is critical to treat ARS, which necessitates identifying diagnostic biomarkers to quickly characterize radiation exposure. Towards this end, a multiplatform metabolomics study was performed to comprehensively characterize the temporal changes in metabolite levels from mice and non-human primate serum samples following γ-irradiation. The metabolomic signature of amifostine was also evaluated in mice as a model for radioprotection. The NMR and mass spectrometry metabolomics analysis identified 23 dysregulated pathways resulting from the radiation exposure. These metabolomic alterations exhibited distinct trajectories within glucose metabolism, phospholipid biosynthesis, and nucleotide metabolism. A return to baseline levels with amifostine treatment occurred for these pathways within a week of radiation exposure. Together, our data suggests a unique physiological change that is independent of radiation dose or species. Furthermore, a metabolic signature of radioprotection was observed through the use of amifostine prophylaxis of ARS.
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影响因子：
45.3
作者：
Brizel, DM;Wasserman, TH;Sauer, R
通讯作者：
Sauer, R
影响因子：
7.7
作者：
Markley JL;Brüschweiler R;Edison AS;Eghbalnia HR;Powers R;Raftery D;Wishart DS
通讯作者：
Wishart DS
影响因子：
13.5
作者：
GLOVER, D;FOX, KR;GLICK, JH
通讯作者：
GLICK, JH
影响因子：
3.6
作者：
Maan, Kiran;Tyagi, Ritu;Rana, Poonam
通讯作者：
Rana, Poonam
影响因子：
2.7
作者：
DiCarlo, Andrea L.;Maher, Carmen;Hick, John L.;Hanfling, Dan;Dainiak, Nicholas;Chao, Nelson;Bader, Judith L.;Coleman, C. Norman;Weinstock, David M.
通讯作者：
Weinstock, David M.