NMR metabolomic study of blood plasma in ischemic and ischemically preconditioned rats: an increased level of ketone bod
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ORIGINAL ARTICLE
NMR metabolomic study of blood plasma in ischemic and ischemically preconditioned rats: an increased level of ketone bodies and decreased content of glycolytic products 24 h after global cerebral ischemia Eva Baranovicova 1 & Marian Grendar 2 & Dagmar Kalenska 3 & Anna Tomascova 3 & Daniel Cierny 4 & Jan Lehotsky 1,3 Received: 25 July 2017 / Accepted: 23 April 2018 # University of Navarra 2018
Abstract Cardiac arrest is one of the leading causes of death among adults in older age. Understanding mechanisms how organism responds to ischemia at global level is essential for the prevention and ischemic patient’s treatment. In this study, we used a global cerebral ischemia induced by four-vessel occlusion as an established animal model for ischemic stroke to investigate metabolic changes after 24 h reperfusion, when transitions occur due to the onset of delayed neuronal death. We also focused on the endogenous phenomenon known as ischemic tolerance by the pre-ischemic treatment. The experiments were carried out on blood plasma samples as easily available and metabolically reflecting the overall changes in injured organism. Our results imply that disturbed glycolysis pathway, as a consequence of ischemic injury, leads to the increased level of ketone bodies (acetone, acetoacetate and β-hydroxybutyrate) along with increased utilization of triacylglycerols in plasma of ischemic and ischemically preconditioned rats. Complementary to, a decreased level of glycolytic intermediates (lactate, pyruvate, acetate) with increased level of glucose was found in ischemic and preconditioned animals. The protective effect of ischemic preconditioning on metabolome recovery was demonstrated by significantly increased level of creatine compared to ischemic, non-preconditioned rats. We also document that acetoacetate, pyruvate, lactate, and leucine have the best discriminatory power between ischemic and control plasma. Conclusively, our results provide evidence that NMR spectra analysis can identify specific group of metabolites present in plasma with the capability for discrimination between individual groups of animals. In addition, an excellent feasibility for the statistical discrimination among ischemic, preconditioned, and control rats can be applied regardless of native or deproteinated plasma and also regardless of noesy or cpmg NMR acquisition.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13105-018-0632-2) contains supplementary material, which is available to authorized users. * Jan Lehotsky [email protected] 1
Division of Neuroscience, Biomedical Center BioMed, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin, Slovakia
2
Bioinformatic Unit, Biomedical Center BioMed, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin, Slovakia
3
Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin, Slovakia
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