Protective Effects of 28-O-Caffeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis

Fang²,

Xu³

et al. 2023

PLoS ONE

Self Cite

The main objective of the present study was to determine metabolic profile changes in the brains of rats after simulated heliox saturated diving (HSD) to 400 meters of sea water compared to the blank controls. Alterations in the polar metabolome in the rat brain due to HSD were investigated in cortex, hippocampus, and striatum tissue samples by applying an NMR-based metabolomic approach coupled with biochemical detection in the cortex. The reduction in glutathione and taurine levels may hypothetically boost antioxidant defenses during saturation diving, which was also proven by the increased malondialdehyde level, the decreased superoxide dismutase, and the decreased glutathione peroxidase in the cortex. The concomitant decrease in aerobic metabolic pathways and anaerobic metabolic pathways comprised downregulated energy metabolism, which was also proven by the biochemical quantification of the metabolic enzymes Na-K ATPase and LDH in cerebral cortex tissue. The significant metabolic abnormalities of amino acid neurotransmitters, such as GABA, glycine, and aspartate, decreased aromatic amino acids, including tyrosine and phenylalanine, both of which are involved in the metabolism of dopamine and noradrenaline, which are downregulated in the cortex. Particularly, a decline in the level of N-acetyl aspartate is associated with neuronal damage. In summary, hyperbaric decompression of a 400 msw HSD affected the brain metabolome in a rat model, potentially including a broad range of disturbing amino acid homeostasis, metabolites related to oxidative stress and energy metabolism, and destabilizing neurotransmitter components. These disturbances may contribute to the neurochemical and neurological phenotypes of HSD.

Section: Multivariate Statistical Analysismentioning

confidence: 99%

Section: System Statistical Metabolic Correlation Analysis and Hierar...mentioning

confidence: 99%

Oxidative stress, dysfunctional energy metabolism, and destabilizing neurotransmitters altered the cerebral metabolic profile in a rat model of simulated heliox saturation diving to 4.0 MPa

Fang²,

Xu³

et al. 2023

PLoS ONE

Self Cite

“…The PCA and PLS-DA score plots were illustrated with the rst and the second principal components (t [1], t [2]), while the OPLS-DA score plot used t [1] and the orthogonal component (to [1]). The parameters Q2 (cum), R2Y(cum), and R2X (cum) were calculated to test the robustness of the discrimination models against over tting [22]. As previously described, a quality assessment value of Q2 ≥ 0.4 is considered a reliable model.…”

Section: Multivariate Statistical Analysismentioning

confidence: 99%

“…Pearson's correlation coe cient calculation and hierarchical cluster analysis were carried out based on the relative integrals of metabolites in R Studio (Version 1.4.1717) with small scripts. For each group pair, the correlation matrix was illustrated in a pixel map as described in the literature [22]. Brie y, for each variable in one group, correlations with p values less than 0.05 were considered signi cant statistical correlations and were kept to construct the nal correlation network to illustrate the latent relationships of metabolites within the group and the disturbed metabolic relationships between groups.…”

Section: System Statistical Metabolic Correlation Analysis and Hierar...mentioning

confidence: 99%

“…During large depth (> 100 msw) saturation diving, the central nervous system is continuously exposed to oxidative stress due to the excessive production of reactive oxygen species (ROS) triggered by the helioxsaturation pressurized environment [24,25]. An imbalance between oxidant and antioxidant levels is a common metabolic regulatory element in various neurological disorders, including Alzheimer's disease [26], autism spectrum disorder [27], ischemic brain [22], traumatic brain injury[28], and so on [19,29,30]. The level changes of SOD, MDA, and Gpx, as recognized indicators for oxidative stress, re ect the oxygen free radical injury in vivo.…”

Section: Oxidative Analysismentioning

confidence: 99%

See 1 more Smart Citation

Oxidative stress, dysfunctional energy metabolism, and destabilizing neurotransmitters altered cerebral metabolic profile in a rat model of a simulated heliox saturation diving to 4.0 Mpa

Fang

et al. 2022

Preprint

Self Cite

A better understanding of the neurological molecular mechanisms induced by an extreme environment of hyperbaric decompression could contribute to the improvement of diving procedures. The main objective of the present study was to determine metabolic profile changes in the brains of rats after simulated heliox saturated diving (HSD) to 400 meters of sea water (msw) (4.0 MPa) with heliox to 5 bar (pO2 = 50 kPa) compared to the blank controls. Alterations in the polar metabolome in the rat brain due to hyperbaric heliox saturation were investigated in cortex, hippocampus, and striatum tissue samples by applying an NMR-based metabolomic approach coupled with biochemical detection in the cortex. The reduction in glutathione and taurine levels may hypothetically boost antioxidant defenses during saturation diving, which was also proven by the increased malondialdehyde level, the decreased superoxide dismutase, and the decreased glutathione peroxidase in the cortex. The concomitant decrease in aerobic metabolic pathways and anaerobic metabolic pathways comprised downregulated energy metabolism, which was also proven by the biochemical quantification of the metabolic enzymes Na-K ATPase and LDH in cerebral cortex tissue. The significant metabolic abnormalities of amino acid neurotransmitters, such as GABA, glycine, and aspartate, decreased aromatic amino acids, including tyrosine and phenylalanine, both of which are involved in the metabolism of dopamine and noradrenaline, which are downregulated in the cortex. In particular, a decline in the level of N-acetyl aspartate is associated with neuronal damage. In summary, hyperbaric decompression of a 400 msw HSD affected the brain metabolome in a rat model, potentially including a broad range of disturbing amino acid homeostasis, metabolites related to oxidative stress and energy metabolism, and destabilizing neurotransmitter components. These disturbances may contribute to the neurochemical and neurological phenotypes of HSD.

Performance comparison of three scaling algorithms in NMR-based metabolomics analysis

Fang

et al. 2023

Open Life Sciences

Unit variance (UV) scaling, mean centering (CTR) scaling, and Pareto (Par) scaling are three commonly used algorithms in the preprocessing of metabolomics data. Based on our NMR-based metabolomics studies, we found that the clustering identification performances of these three scaling methods were dramatically different as tested by the spectra data of 48 young athletes’ urine samples, spleen tissue (from mice), serum (from mice), and cell (from Staphylococcus aureus) samples. Our data suggested that for the extraction of clustering information, UV scaling could serve as a robust approach for NMR metabolomics data for the identification of clustering analysis even with the existence of technical errors. However, for the purpose of discriminative metabolite identification, UV scaling, CTR scaling, and Par scaling could equally extract discriminative metabolites efficiently based on the coefficient values. Based on the data presented in this study, we propose an optimal working pipeline for the selection of scaling algorithms in NMR-based metabolomics analysis, which has the potential to serve as guidance for junior researchers working in the NMR-based metabolomics research field.