Screening of Lipids for Early Triage and Dose Estimation after Acute Radiation Exposure in Rat Plasma Based on Targeted Lipidomics Analysis

Xi, Cong; Hua, Zhao; Lü, Xue; Cai, Tian-Jing; Li, Shuang; Liu, Kehui; Tian, Mei; Liu, Qingjie

doi:10.1021/acs.jproteome.0c00560

Cited by 10 publications

(7 citation statements)

References 43 publications

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“…Several untargeted lipidomic studies have investigated irradiation effects in several models including cell cultures [23], murines [12,[24][25][26], NHPs [27][28][29], and humans [30] while the initial targeted lipidomic studies have primarily been limited to commercially available kits or eicosanoid profiling [31][32][33][34][35]. More recently, targeted lipid studies utilizing multiplex MRM assays showed that combinations from 416 lipids in blood could be used for modelling IR exposure between 4-72 h for 0-8 Gy in rats with excellent sensitivity and specificity [36]. As we typically see an increased number of lipid compounds changes post-irradiation in serum vs. polar compounds, we chose to utilize a targeted lipidomics approach in the current study.…”

Section: Targeted Lipidomics: Serummentioning

confidence: 99%

“…Polyunsaturated (PUFA) CEs, typically containing 18:2, 20:4, or 22:6 acyl chains, can also be enzymatically or non-enzymatically oxidized and can form more complex peroxides [40]. Previous experiments have reported perturbation to CE(20:4) and CE(22:6) levels at higher doses in NHPs (10 Gy) and rats (8 Gy) [27,36] with a temporal change in NHPs showing lower concentrations at earlier time points (4 h), then increasing at later time points (7-10 d) [28]. These changes may be partially dose rate dependent, as in this study we observed increases in CE(22:6) at 1 d following the reference dose rate exposure and a decrease in CE(20:4) following the VHDR exposure (Supplementary File S1).…”

Section: Targeted Lipidomics: Serummentioning

confidence: 99%

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Biofluid Metabolomics and Lipidomics of Mice Exposed to External Very High-Dose Rate Radiation

et al. 2022

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High-throughput biodosimetry methods to determine exposure to ionizing radiation (IR) that can also be easily scaled to multiple testing sites in emergency situations are needed in the event of malicious attacks or nuclear accidents that may involve a substantial number of civilians. In the event of an improvised nuclear device (IND), a complex IR exposure will have a very high-dose rate (VHDR) component from an initial blast. We have previously addressed low-dose rate (LDR, ≤1 Gy/day) exposures from internal emitters on biofluid small molecule signatures, but further research on the VHDR component of the initial blast is required. Here, we exposed 8- to 10-week-old male C57BL/6 mice to an acute dose of 3 Gy using a reference dose rate of 0.7 Gy/min or a VHDR of 7 Gy/s, collected urine and serum at 1 and 7 d, then compared the metabolite signatures using either untargeted (urine) or targeted (serum) approaches with liquid chromatography mass spectrometry platforms. A Random Forest classification approach showed strikingly similar changes in urinary signatures at 1 d post-irradiation with VHDR samples grouping closer to control samples at 7 d. Identical metabolite panels (carnitine, trigonelline, xanthurenic acid, N6,N6,N6-trimethyllysine, spermine, and hexosamine-valine-isoleucine-OH) could differentiate IR exposed individuals with high sensitivity and specificity (area under the receiver operating characteristic (AUROC) curves 0.89–1.00) irrespective of dose rate at both days. For serum, the top 25 significant lipids affected by IR exposure showed slightly higher perturbations at 0.7 Gy/min vs. 7 Gy/s; however, identical panels showed excellent sensitivity and specificity at 1 d (three hexosylceramides (16:0), (18:0), (24:0), sphingomyelin [26:1], lysophosphatidylethanolamine [22:1]). Mice could not be differentiated from control samples at 7 d for a 3 Gy exposure based on serum lipid signatures. As with LDR exposures, we found that identical biofluid small molecule signatures can identify IR exposed individuals irrespective of dose rate, which shows promise for more universal applications of metabolomics for biodosimetry.

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Section: Targeted Lipidomics: Serummentioning

confidence: 99%

Section: Targeted Lipidomics: Serummentioning

confidence: 99%

Biofluid Metabolomics and Lipidomics of Mice Exposed to External Very High-Dose Rate Radiation

et al. 2022

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“…Modifications of radiation effects can be observed by lipid peroxidation [152]. Radiation biodosimetry is another developing field and radiation-responsive lipids biomarkers identified in lipidomics studies are important in this development [153]. A recent study has investigated seven radiation-responsive lipids, including PC (18:2/18:2), PC (18:0/18:2), Lyso PC 18:1, PC (18:0/20:4), SM (D18:0/24:1), PC (16:0/18:1), and Lyso PC 18:2 which are useful in radiation biodosimeters [154].…”

Section: Lipidomicsmentioning

confidence: 99%

Multi-Omics Approaches and Radiation on Lipid Metabolism in Toothed Whales

Senevirathna

Asakawa

2021

Life

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Lipid synthesis pathways of toothed whales have evolved since their movement from the terrestrial to marine environment. The synthesis and function of these endogenous lipids and affecting factors are still little understood. In this review, we focused on different omics approaches and techniques to investigate lipid metabolism and radiation impacts on lipids in toothed whales. The selected literature was screened, and capacities, possibilities, and future approaches for identifying unusual lipid synthesis pathways by omics were evaluated. Omics approaches were categorized into the four major disciplines: lipidomics, transcriptomics, genomics, and proteomics. Genomics and transcriptomics can together identify genes related to unique lipid synthesis. As lipids interact with proteins in the animal body, lipidomics, and proteomics can correlate by creating lipid-binding proteome maps to elucidate metabolism pathways. In lipidomics studies, recent mass spectroscopic methods can address lipid profiles; however, the determination of structures of lipids are challenging. As an environmental stress, the acoustic radiation has a significant effect on the alteration of lipid profiles. Radiation studies in different omics approaches revealed the necessity of multi-omics applications. This review concluded that a combination of many of the omics areas may elucidate the metabolism of lipids and possible hazards on lipids in toothed whales by radiation.

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“…Glycerophospholipids (GP) and sphingolipids (SL) that include a choline group have essential structural and signaling functions [ 14 , 15 ]. These classes of lipids were already shown to be affected in response to ionizing radiation, both local body RT in humans [ 16 ] and whole-body irradiation in rodents [ 17 ]. Our previous study on lipid mass profiling documented that serum levels of different phospholipids were affected in samples of HNSCC patients treated with IMRT using the continuous accelerated irradiation (CAIR) scheme.…”

Section: Introductionmentioning

confidence: 99%

Dose-dependence of radiotherapy-induced changes in serum levels of choline-containing phospholipids; the importance of lower doses delivered to large volumes of normal tissues

et al. 2021

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Background Conformal radiotherapy is a primary treatment in head and neck cancer, which putative adverse effects depend on relatively low doses of radiation delivered to increased volumes of normal tissues. Systemic effects of such treatment include radiation-induced changes in serum lipid profile, yet dose- and volume-dependence of these changes remain to be established. Methods Here we analyzed levels of choline-containing phospholipids in serum samples collected consecutively during the radiotherapy used as the only treatment modality. The liquid chromatography–mass spectrometry (LC-MS) approach applied in the study enabled the detection and quantitation of 151 phospholipids, including (lyso)phosphatidylcholines and sphingomyelins. Results No statistically significant differences were found in the pretreatment samples from patients with different locations and stages of cancer. To compensate for potential differences between schemes of radiotherapy, the biologically effective doses were calculated and used in the search of correlations with specific lipid levels. We found that the levels of several phospholipids depended on the maximum dose delivered to the gross tumor volume and total radiation energy absorbed by the patient’s body. Increased doses correlated with increased levels of sphingomyelins and reduced levels of phosphatidylcholines. Furthermore, we observed several phospholipids whose serum levels correlated with the degree of acute radiation toxicity. Conclusion Noteworthy, serum phospholipid levels were associated mainly with volumes of normal tissues irradiated with relatively low doses (i.e., total accumulated dose 20 Gy), which indicated the importance of such effects on the systemic response of the patient’s organism to intensity-modulated radiotherapy (IMRT).

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Screening of Lipids for Early Triage and Dose Estimation after Acute Radiation Exposure in Rat Plasma Based on Targeted Lipidomics Analysis

Cited by 10 publications

References 43 publications

Biofluid Metabolomics and Lipidomics of Mice Exposed to External Very High-Dose Rate Radiation

Biofluid Metabolomics and Lipidomics of Mice Exposed to External Very High-Dose Rate Radiation

Multi-Omics Approaches and Radiation on Lipid Metabolism in Toothed Whales

Dose-dependence of radiotherapy-induced changes in serum levels of choline-containing phospholipids; the importance of lower doses delivered to large volumes of normal tissues

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