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ABSTRACT: Abstract Purpose: In the classical description of acute radiation syndrome, the role of central nervous system (CNS) is underestimated. It is now well recognised that ionising radiation induced oxidative stress may bring about functional changes in brain. In this study, we prospectively evaluated metabolic changes in brain after whole body irradiation in mice using in vivo proton (1H) nuclear magnetic resonance spectroscopy (MRS). Material and Methods: Young adult mice were exposed to whole body irradiation of 8 Gy and controls were sham irradiated. In vivo (1)H MRS from cortex-hippocampus and hypothalamic-thalamic region of brain at different time points i.e as early as 6 hours, day 1, 2, 3, 5 and 10 post irradiation was carried out at 7 Tesla animal magnetic resonance imaging system. Brain metabolites were measured and quantitative analysis of detectable metabolites was performed by linear combination of model (LCModel). Results: Significant reduction in myoinositol (p=0.03) and taurine (p=0.02) ratios were observed in cortex-hippocampus region as early as day 2 post irradiation compared to controls. These metabolic alterations remained sustained over day 10 post irradiation. Conclusions: The results of this preliminary study suggest that the alteration/reduction in the mI and Tau concentration may be associated with physiological perturbations in astrocytes or radiation induced neuro-inflammatory response triggered in microglial cell.
International Journal of Radiation Biology 10/2012; · 2.28 Impact Factor
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ABSTRACT: The nuclear arsenal and the use of nuclear technologies have enhanced the likelihood of whole-body/partial-body radiation exposure. The central nervous system is highly susceptible to even low doses of radiation. With the aim of detecting and monitoring the pathologic changes of radiation-induced damage in brain parenchyma, we used serial diffusion tensor magnetic resonance imaging (DTI) with a 7T magnetic resonance unit and neurobehavioral assessments mice irradiated with 3-, 5-, and 8-Gy doses of radiation. Fractional anisotropy (FA) and mean diffusivity (MD) values at each time point (baseline, day 1, day 5, and day 10) were quantified from hippocampus, thalamus, hypothalamus, cudate-putamen, frontal cortex, sensorimotor cortex, corpus callosum, cingulum, and cerebral peduncle. Behavioral tests were performed at baseline, day 5, and day 10. A decrease in FA values with time was observed in all three groups. At day 10, dose-dependent decreases in FA and MD values were observed in all of the regions compared with baseline. Behavioral data obtained in this study correlate with FA values. Radiation-induced affective disorders were not radiation dose dependent, insofar as the anxiety-like symptoms at the lower dose (3 Gy) mimics to the symptoms with the higher dose (8 Gy) level but not with the moderate dose. However, there was a dose-dependent decline in cognitive function as well as FA values. Behavioral data support the DTI indices, so it is suggested that DTI may be a useful tool for noninvasive monitoring of radiation-induced brain injury.
Journal of Neuroscience Research 05/2012; 90(10):2009-19. · 2.74 Impact Factor
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ABSTRACT: 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 1H nuclear magnetic resonance (1H NMR) spectroscopy and pattern recognition (PR) technique. The 1H 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, α 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 1H 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.
KeywordsRadiation sickness–
1H NMR spectroscopy–Serum–Urine–Metabonomics
Metabolomics 05/2012; 7(4):583-592. · 4.51 Impact Factor
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ABSTRACT: Heavy metals are known for their associated nephrotoxicity and nickel is no exception. An integrated metabonomic approach, based on high-resolution 1H NMR spectroscopy, was applied to determine the acute biochemical effects of NiCl2 on the renal tissues of rats. Kidney homogenates from rats treated with NiCl2 at two dose levels (4 and 20 mg kg−1 b.w., i.p.) and those from controls were analysed using 1H NMR spectroscopy and also assessed for antioxidant parameters at days 1, 3 and 5 post-dose. The major metabolite changes corresponding to nickel exposure were related to amino acids, osmolytes and energy metabolites. Differential responses were observed in 1H NMR spectra with exposure to low and high doses of NiCl2. For high doses, 1H NMR spectral analysis revealed alterations in renal tissues, along with damage to the cortical and papillary region and depletion of renal osmolytes such as betaine, trimethyl amine oxide, myo-inositol and taurine, which persisted until day 5 post-dose. The metabolite profile of 1H NMR spectra obtained from animals treated with lower dose of NiCl2 initially increased as an immediate stress response and then showed signs of recovery with the passage of time. NMR spectral analysis was well corroborated with histopathological and oxidative stress results. Nickel-induced oxidative stress was observed in both groups of animals with increased levels of antioxidant parameters at initial time points, but continued to increase in the high-dose group. The present study shows a huge potential of metabonomics for mapping organ-based metabolic response during heavy metal toxicity. Copyright © 2011 John Wiley & Sons, Ltd.
Journal of Applied Toxicology 09/2011; · 2.48 Impact Factor
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ABSTRACT: Thallium (Tl) is a toxic heavy metal and its exposure to the human body causes physiological and biochemical changes due to its interference with potassium-dependent biological reactions. A high-resolution (1)H NMR spectroscopy based metabonomic approach has been applied for investigating acute biochemical effects caused by thallium sulfate (Tl(2)SO(4)). Male strain A mice were divided in three groups and received three doses of Tl(2)SO(4) (5, 10 and 20 mg kg(-1) b.w., i.p.). Urine samples collected at 3, 24, 72 and 96 h post-dose time points were analyzed by (1)H NMR spectroscopy. NMR spectral data were processed and analyzed using principal components analysis to represent biochemical variations induced by Tl(2)SO(4). Results showed Tl-exposed mice urine to have distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of treated groups. The metabolic signature of urine analysis from Tl(2)SO(4)-treated animals exhibited an increase in the levels of creatinine, taurine, hippurate and β-hydroxybutyrate along with a decrease in energy metabolites trimethylamine and choline. These findings revealed Tl-induced disturbed gut flora, membrane metabolite, energy and protein metabolism, representing physiological dysfunction of vital organs. The present study indicates the great potential of NMR-based metabonomics in mapping metabolic response for toxicology, which could ultimately lead to identification of potential markers for Tl toxicity.
Journal of Applied Toxicology 01/2011; 31(7):663-70. · 2.48 Impact Factor
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ABSTRACT: Radiation exposure induces change in many biological compounds. It is important to assess the physiological and biochemical response to an absorbed dose of ionising radiation due to intentional or accidental event and to predict medical consequences for medical management. In the present study, nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling was used in mice serum for identification of radiation-induced changes at metabolite level.
Mice were irradiated with 3, 5 and 8 Gray of γ-radiation dose and serum samples collected at day 1, 3 and 5 post irradiation were analysed by proton nuclear magnetic resonance (¹H NMR) spectroscopy. ¹H NMR spectra of serum were analysed by pattern recognition using principal component analysis.
Irradiated mice serum showed distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of irradiated groups. ¹H NMR spectral analysis exhibited increased lactate, amino acids, choline and lipid signals as well as decreased glucose signals. These findings indicate radiation-induced disturbed energy, lipid and protein metabolism.
The information obtained from this study reflects multiple physiological dysfunctions. The study promises the application of NMR-based metabonomics in the field of radiobiology, for development of metabolic-based markers for screening of risk populations and medical management in these cases.
International Journal of Radiation Biology 11/2010; 87(1):91-7. · 2.28 Impact Factor
