Nuclear magnetic resonance spectroscopy-based metabonomic investigation of biochemical effects in serum of γ-irradiated mice

Khan, Asia; Rana, Poonam; Devi, M. Memita; Chaturvedi, Shubhra; Javed, Salim; Tripathi, Renu; Khushu, Subash

doi:10.3109/09553002.2010.518211

Cited by 48 publications

(42 citation statements)

References 27 publications

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“…These and other energy metabolites represent bioenergetic status of the body and might have resulted from increased energy demands and were, therefore, suggestive of changes in energy metabolism after radiation exposure (Lerman et al 1962). Dose dependent acute effects of radiation showing altered membrane and energy metabolism in serum have been reported in our earlier study (Khan et al 2010). In this study, highest increase in the energy intermediates was observed at 6 h post dose in urine samples.…”

Section: Resultssupporting

confidence: 58%

“…Serum and urine samples provide a well established surrogate medium for the study of metabolic physiological functions of not only liver and kidney, but also for other vital organs. Earlier studies in the field of radiation metabolomics have shown time and dose dependent changes due to acute radiation stress in animal model and cell system (Tyburski et al 2008;Lanz et al 2009;Patterson et al 2009;Wang et al 2009;Khan et al 2010). However, metabolic changes during different phases of radiation sickness are yet to be elucidated.…”

Section: Introductionmentioning

confidence: 96%

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NMR spectroscopy based metabolic profiling of urine and serum for investigation of physiological perturbations during radiation sickness

et al. 2011

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Radiation accidents are rare events that induce radiation syndrome, a complex pathology which is difficult to treat. In medical management of radiation victims, life threatening damage to different physiological systems should be taken into consideration. The present study was proposed to identify metabolic and physiological perturbations in biofluids of mice during different phases of radiation sickness using 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy and pattern recognition (PR) technique. The 1 H NMR spectra of the biofluids collected from mice irradiated with 5 Gray (Gy) at different time points during radiation sickness were analysed visually and by principal components analysis. Urine and serum spectral profile clearly showed altered metabolic profiles during different phases of radiation sickness. Increased concentration of urine metabolites viz. citrate, a ketoglutarate, succinate, hippurate, and trimethylamine during prodromal and clinical manifestation phase of radiation sickness shows altered gut microflora and energy metabolism. On the other hand, serum nuclear magnetic resonance (NMR) spectra reflected changes associated with lipid, energy and membrane metabolism during radiation sickness. The metabonomic time trajectory based on PR analysis of 1 H NMR spectra of urine illustrates clear separation of irradiated mice group at different time points from pre dose. The difference in NMR spectral profiles depicts the pathophysiological changes and metabolic disturbances observed during different phases of radiation sickness, that in turn, demonstrate involvement of multiple organ dysfunction. This could further be useful in development of multiparametric approach for better evaluation of radiation damage as well as for medical management during radiation sickness.

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Section: Resultssupporting

confidence: 58%

Section: Introductionmentioning

confidence: 96%

NMR spectroscopy based metabolic profiling of urine and serum for investigation of physiological perturbations during radiation sickness

et al. 2011

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“…Possible explanations for shifts in amino acid serum concentrations have been protein breakdown, altered amino acid metabolism, diet shifts, cell death, and damage to kidneys and intestinal lining. 10,17,19,22,32 …”

Section: Discussionmentioning

confidence: 99%

“…Within the field of radiation metabolomics, past studies have primarily utilized liquid chromatography (LC) mass spectrometry (MS), 5,8,11,13–18 with less attention given to gas chromatography (GC) MS 7,19–21 and nuclear magnetic resonance (NMR) platforms. 22 GC–MS is a well-established bioanalytical platform ideal for detecting myriad molecules including volatile small metabolites, isomeric compounds, derivatized organic acids, and carbohydrates. 23 Many of these compounds are vital in energy metabolism (e.g., Warburg effect) and are difficult to analyze by LC–MS because of their inherent chemical properties (e.g., chromatographic separation of isomers).…”

Section: Introductionmentioning

confidence: 99%

Gas Chromatography/Mass Spectrometry Metabolomics of Urine and Serum from Nonhuman Primates Exposed to Ionizing Radiation: Impacts on the Tricarboxylic Acid Cycle and Protein Metabolism

et al. 2017

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Ionizing radiation (IR) directly damages cells and tissues or indirectly damages them through reactive free radicals that may lead to longer term adverse sequelae such as cancers, persistent inflammation, or possible death. Potential exposures include nuclear reactor accidents, improper disposal of equipment containing radioactive materials or medical errors, and terrorist attacks. Metabolomics (comprehensive analysis of compounds <1 kDa) by mass spectrometry (MS) has been proposed as a tool for high-throughput biodosimetry and rapid assessment of exposed dose and triage needed. While multiple studies have been dedicated to radiation biomarker discovery, many have utilized liquid chromatography (LC) MS platforms that may not detect particular compounds (e.g., small carboxylic acids or isomers) that complementary analytical tools, such as gas chromatography (GC) time-of-flight (TOF) MS, are ideal for. The current study uses global GC-TOF-MS metabolomics to complement previous LC–MS analyses on nonhuman primate biofluids (urine and serum) 7 days after exposure to 2, 4, 6, 7, and 10 Gy IR. Multivariate data analysis was used to visualize differences between control and IR exposed groups. Univariate analysis was used to determine a combined 26 biomarkers in urine and serum that significantly changed after exposure to IR. We found several metabolites involved in tricarboxylic acid cycle function, amino acid metabolism, and host microbiota that were not previously detected by global and targeted LC–MS studies.

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“…Moreover, exposure to artificial radiation has increased due to its use in cancer therapy, medical test equipment (such as X-ray-emitting computed tomography (CT) scanners), waste from the nuclear power industry, and nuclear accidents [1]. Excessive exposure to radiation causes serious health problems, because the effects include a series of molecular-, cellular-, and tissue-level processes [2].…”

Section: Introductionmentioning

confidence: 99%

Dose-Dependent Metabolic Alterations in Human Cells Exposed to Gamma Irradiation

Kwon

Bae

et al. 2014

PLoS ONE

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Radiation exposure is a threat to public health because it causes many diseases, such as cancers and birth defects, due to genetic modification of cells. Compared with the past, a greater number of people are more frequently exposed to higher levels of radioactivity today, not least due to the increased use of diagnostic and therapeutic radiation-emitting devices. In this study, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS)-based metabolic profiling was used to investigate radiation- induced metabolic changes in human fibroblasts. After exposure to 1 and 5 Gy of γ-radiation, the irradiated fibroblasts were harvested at 24, 48, and 72 h and subjected to global metabolite profiling analysis. Mass spectral peaks of cell extracts were analyzed by pattern recognition using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The results showed that the cells irradiated with 1 Gy returned to control levels at 72 h post radiation, whereas cells irradiated with 5 Gy were quite unlike the controls; therefore, cells irradiated with 1 Gy had recovered, whereas those irradiated with 5 Gy had not. Lipid and amino acid levels increased after the higher-level radiation, indicating degradation of membranes and proteins. These results suggest that MS-based metabolite profiling of γ-radiation-exposed human cells provides insight into the global metabolic alterations in these cells.

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Nuclear magnetic resonance spectroscopy-based metabonomic investigation of biochemical effects in serum of γ-irradiated mice

Cited by 48 publications

References 27 publications

NMR spectroscopy based metabolic profiling of urine and serum for investigation of physiological perturbations during radiation sickness

NMR spectroscopy based metabolic profiling of urine and serum for investigation of physiological perturbations during radiation sickness

Gas Chromatography/Mass Spectrometry Metabolomics of Urine and Serum from Nonhuman Primates Exposed to Ionizing Radiation: Impacts on the Tricarboxylic Acid Cycle and Protein Metabolism

Dose-Dependent Metabolic Alterations in Human Cells Exposed to Gamma Irradiation

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