Plasma metabolomic signatures from patients following high-dose total body irradiation

Hong, Xiedong; Liu, Tian; Wu, Qiong; Gu, Linxia; Wang, Wenli; Wu, Hanxu; Zhao, Mingxiao; Wu, Xiaojin; Wang, Chang

doi:10.1039/d2mo00274d

Cited by 2 publications

(3 citation statements)

References 77 publications

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“…In nonhuman primates, diversity was observed in estrogen receptor signaling and differential expression of genes in the jejunum when comparing sex and countermeasure treatment in total and partial body irradiation (PBI) models [Vellichirammal et al, 2023]. A recent study in human patients undergoing myeloablative TBI revealed a panel of 4 differential expressed metabolites, namely, phosphatidylcholine, urate, ornithine, and glycochenodeoxycholate-3-sulfate [Hong et al, 2023].…”

Section: Introductionmentioning

confidence: 99%

Sex as a Factor in Murine Radiation Research: Implications for Countermeasure Development

Holmes-Hampton,

Kumar,

Valenzia

et al. 2023

Cytogenet Genome Res

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There is an increased threat of exposure to ionizing radiation, in the event of such exposure the availability of medical countermeasures will be vital to ensure the protection of the population. Effective countermeasures should be efficacious across a varied population and most importantly amongst both males and females. Radiation research must be conducted in animal models which act as a surrogate for the human response. Here we identify differences in survival in male and female C57BL/6 in both a total body irradiation (TBI) model using the Armed Forces Radiobiology Research Institute (AFRRI) 60Co source and a partial body irradiation (PBI) model using the AFRRI Linear Accelerator (LINAC) with 4MV photons and 2.5% bone marrow shielding. In both models we observed a higher degree of radioresistance in female animals and a corresponding radiosensitivity in males. One striking difference in male and female rodents is body size/weight and we investigated the role of pre-irradiation body weight on survivability for animals irradiated at the same dose of irradiation (8 Gy TBI, 14 Gy PBI). We found that weight does not influence survival in the TBI model and that heavier males but lighter females have increased survival in the PBI model. This incongruence in survival amongst the sexes should be taken into consideration in the course of developing radiation countermeasures for response to a mass casualty incident.

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Section: Introductionmentioning

confidence: 99%

Sex as a Factor in Murine Radiation Research: Implications for Countermeasure Development

Holmes-Hampton,

Kumar,

Valenzia

et al. 2023

Cytogenet Genome Res

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“…As essential amino acids, branched-chain amino acids (BCAAs, leucine, isoleucine and valine) are widely studied due to their crucial role in the regulation of protein synthesis, primarily through the activation of the mTOR signaling pathway and their growing recognition as players in the regulation of a variety of physiological and metabolic processes [ 29 , 30 ]. Elevated blood BCAA levels in both animal models and humans following total body irradiation (TBI) have been implicated in radiation-induced activated protein breakdown [ 13 , 22 , 31 , 32 ]. In contrast to the above findings, BCAAs showed obvious reduced levels in both lung tissues and plasma in response to WTI ( Figure S9 ).…”

Section: Discussionmentioning

confidence: 99%

“…To meet the demands of rapid radiation damage assessment in large-scale nuclear accidents, metabolomics has been attempted to identify biomarkers of radiation injury in various biological samples. Although the majority of studies have focused on a variety of biofluids derived from animal models (like mice, rats and non-human primates), as well as humans, the overlap in biomarkers of radiation injury across species has highlighted the metabolic pathways that are most perturbed, including β-oxidation of fatty acids (acylcarnitines), energy metabolism (TCA cycle intermediates), purines and pyrimidines metabolism, pro-inflammatory pathways (the omega-6 constituents, polyunsaturated fatty acids) and amino acids metabolism [ 10 , 11 , 12 , 13 , 14 ]. In the case of RILI, metabolomics has been utilized to reveal the metabolic characteristics of RILI in different genotypes of mice [ 15 ] and to explore the metabolic changes in serum and lung tissues exposed to irradiation [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Signatures Associated with Radiation-Induced Lung Injury by Correlating Lung Tissue to Plasma in a Rat Model

Gu,

Wang,

et al. 2023

Metabolites

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The lung has raised significant concerns because of its radiosensitivity. Radiation-induced lung injury (RILI) has a serious impact on the quality of patients’ lives and limits the effect of radiotherapy on chest tumors. In clinical practice, effective drug intervention for RILI remains to be fully elucidated. Therefore, an in-depth understanding of the biological characteristics is essential to reveal the mechanisms underlying the complex biological processes and discover novel therapeutic targets in RILI. In this study, Wistar rats received 0, 10, 20 or 35 Gy whole-thorax irradiation (WTI). Lung and plasma samples were collected within 5 days post-irradiation. Then, these samples were processed using liquid chromatography–mass spectrometry (LC-MS). A panel of potential plasma metabolic markers was selected by correlation analysis between the lung tissue and plasma metabolic features, followed by the evaluation of radiation injury levels within 5 days following whole-thorax irradiation (WTI). In addition, the multiple metabolic dysregulations primarily involved amino acids, bile acids and lipid and fatty acid β-oxidation-related metabolites, implying disturbances in the urea cycle, intestinal flora metabolism and mitochondrial dysfunction. In particular, the accumulation of long-chain acylcarnitines (ACs) was observed as early as 2 d post-WTI by dynamic plasma metabolic data analysis. Our findings indicate that plasma metabolic markers have the potential for RILI assessment. These results reveal metabolic characteristics following WTI and provide new insights into therapeutic interventions for RILI.

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Plasma metabolomic signatures from patients following high-dose total body irradiation

Abstract: Despite some advances in the study of radiation injuries, effective methods of prevention and treatment of severe acute radiation syndrome or illness (ARS) are still lacking. Therefore, an in-depth understanding...

Cited by 2 publications

References 77 publications

Sex as a Factor in Murine Radiation Research: Implications for Countermeasure Development

Sex as a Factor in Murine Radiation Research: Implications for Countermeasure Development

Metabolomic Signatures Associated with Radiation-Induced Lung Injury by Correlating Lung Tissue to Plasma in a Rat Model

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