Time‐related metabolomics study in the rat plasma after global cerebral ischemia and reperfusion: Effect of ischemic preconditioning

Baranovičová, Eva; Kalenská, Dagmar; Tomašcová, Anna; Holubcikova, Simona; Lehotský, Ján

doi:10.1002/iub.2340

Cited by 9 publications

(26 citation statements)

References 64 publications

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“…It is remarkable that observed metabolomic changes, in particular increased glucose and decreased pyruvate and alanine, tryptophane and tyrosine balanced with increased ketone bodies are very similar to those found in rats after ischemia [36][37][38] and in patients after myocardial infarction [39].…”

Section: Discussionsupporting

confidence: 55%

“…Taking together, observed metabolomic changes in patients with primary and secondary lung cancer are the superposition of changes caused by the presence of cancer and changes similar to those observed after ischemia, where the second ones appear to be dominant in the statistical discrimination. Here it is important to note, that metabolites that were of the highest discrimination power (section 3) cannot be connected primarily to lung cancer, as they were strongly overlapping with those differencing subjects after ischemic injury from controls [36][37][38][39].…”

Section: Discussionmentioning

confidence: 99%

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Metabolomic profiling of blood plasma of patients with lung cancer and malignant tumors with metastasis in the lungs showed similar features and promising statistical discrimination against controls

Šarlinová

Baranovičová

Skaličanová

et al. 2021

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Targeting metabolomic pathways is a promising strategy for cancer treatment. Alterations in the metabolomic state have also an epigenetic impact making the metabolomic studies even more interesting. We explored metabolomic changes in blood plasma of patients with primary and secondary lung cancer and tried to explore their origin. We also applied a discrimination algorithm on the data. In the study, blood samples from 132 patients with primary lung cancer, 47 with secondary lung cancer, and 77 subjectively healthy subjects without any cancer history were used.The samples were measured by NMR spectroscopy. PCA and PLSDA analyzes did not distinguish between patients with primary and secondary lung tumors. Accordingly, no significantly changed levels of plasmatic metabolites were found between these groups. When comparing with healthy controls, significantly increased glucose, citrate, acetate, 3-hydroxybutyrate, and creatinine balanced with decreased pyruvate, lactate, alanine, tyrosine, and tryptophan were found as a common feature of both groups. Metabolomic analysis of blood plasma showed considerable proximity of patients with primary and secondary lung cancer. The changes observed can be partially explained as cancer-derived and also as changes showing ischemic nature. Random Forrest discrimination based on the relative concentration of metabolites in blood plasma performed very promising with AUC of 0.95 against controls; however noticeable parts of differencing metabolites are overlapping with those observed after ischemic injury in other studies.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling of blood plasma of patients with lung cancer and malignant tumors with metastasis in the lungs showed similar features and promising statistical discrimination against controls

Šarlinová

Baranovičová

Skaličanová

et al. 2021

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“…global cerebral ischemia showed lower extent of observed postischemic changes in a number of metabolites in both tissue extracts. This is in line of partially protected cerebral histo-morphological patterns [3,24,25]. In hippocampus, the relative concentrations of almost all metabolites responded by full or partial restoration, when IPC was introduced.…”

Section: Protective Effect Of Ischemic Preconditioning In Brain Tissue Extractssupporting

confidence: 73%

Metabolomic Recovery as a Result of Ischemic Preconditioning Was More Pronounced in Hippocampus than in Cortex That Appeared More Sensitive to Metabolomic Blood Components

et al. 2021

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The study of an organism’s response to ischemia at different levels is essential to understand the mechanism of the injury as well as protection. We used the occlusion of four vessels as an animal model of global cerebral ischemia to investigate metabolic alterations in cerebral cortex, hippocampus, blood plasma, as well as in a remote organ, the heart, in rats undergoing 24 h postischemic reperfusion. By inducing sublethal ischemic stimuli, we focused on endogenous phenomena known as ischemic tolerance that is currently the best known and most effective way of protecting against ischemic injury. NMR spectroscopy was used to analyze relative metabolite levels in homogenates from rats’ cerebral cortex, hippocampus, and heart together with deproteinized blood plasma. In individual animals subjected to global cerebral ischemia, relative concentrations of the essential amino acids isoleucine, valine, phenylalanine, and tyrosine in cerebral cortex correlated with those in blood plasma (p < 0.05, or boundary significant p < 0.09). This did not apply for the hippocampus, suggesting a closer relation between ischemic cortex and metabolomic blood components. Hippocampal non-participation on correlation with blood components may emphasize the observed partial or full normalization the post-ischemically altered levels of a number of metabolites in the preconditioned animals. Remarkably, that was observed for cortex to a lesser extent. As a response to the global cerebral ischemia in heart tissue, we observed decreased glutamate and increased 3-hydroxybutyrate. Ischemically induced semi-ketotic state and other changes found in blood plasma partially normalized when ischemic preconditioning was introduced. Some metabolomic changes were so strong that even individual metabolites were able to differentiate between ischemic, ischemically preconditioned, and control brain tissues.

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“…From 22 evaluated metabolites (lactate, glutamine, histidine, isoleucine, leucine, lysine, phenylalanine, threonine, tryptophan, tyrosine, valine, pyruvate, citrate, acetate, alanine, glucose, succinate, 3-hydroxybutyrate, 2-oxoisocaproate, 2-oxoisovalerate, 3-methyl-2-oxovalerate and lipoproteins fraction (composition please see [ 29 , 30 ]), plasma levels of eight metabolites: glucose, acetate, 3-hydroxybutyrate, phenylalanine, tryptophan, tyrosine, histidine and lipoproteins fraction were significantly changed in rats subjected to Met diet administration against controls. Changes observed in plasma levels of three metabolites: leucine, isoleucine and valine were approaching the borderline of significance with a p < 0.08.…”

Section: Resultsmentioning

confidence: 99%

“…The whole procedure regarding blood sampling, plasma deproteinization, NMR measurement, data processing, evaluation and statistical analysis was carried out identically with our previous work [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats

Kovalská

Baranovičová

Kalenská

et al. 2021

IJMS

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L-methionine, an essential amino acid, plays a critical role in cell physiology. High intake and/or dysregulation in methionine (Met) metabolism results in accumulation of its intermediate(s) or breakdown products in plasma, including homocysteine (Hcy). High level of Hcy in plasma, hyperhomocysteinemia (hHcy), is considered to be an independent risk factor for cerebrovascular diseases, stroke and dementias. To evoke a mild hHcy in adult male Wistar rats we used an enriched Met diet at a dose of 2 g/kg of animal weight/day in duration of 4 weeks. The study contributes to the exploration of the impact of Met enriched diet inducing mild hHcy on nervous tissue by detecting the histo-morphological, metabolomic and behavioural alterations. We found an altered plasma metabolomic profile, modified spatial and learning memory acquisition as well as remarkable histo-morphological changes such as a decrease in neurons’ vitality, alterations in the morphology of neurons in the selective vulnerable hippocampal CA 1 area of animals treated with Met enriched diet. Results of these approaches suggest that the mild hHcy alters plasma metabolome and behavioural and histo-morphological patterns in rats, likely due to the potential Met induced changes in “methylation index” of hippocampal brain area, which eventually aggravates the noxious effect of high methionine intake.

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Time‐related metabolomics study in the rat plasma after global cerebral ischemia and reperfusion: Effect of ischemic preconditioning

Cited by 9 publications

References 64 publications

Metabolomic profiling of blood plasma of patients with lung cancer and malignant tumors with metastasis in the lungs showed similar features and promising statistical discrimination against controls

Metabolomic profiling of blood plasma of patients with lung cancer and malignant tumors with metastasis in the lungs showed similar features and promising statistical discrimination against controls

Metabolomic Recovery as a Result of Ischemic Preconditioning Was More Pronounced in Hippocampus than in Cortex That Appeared More Sensitive to Metabolomic Blood Components

Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats

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