scholarly journals Investigation of the idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. through metabolomics using GC-MS

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yan Lin ◽  
Rong Xiao ◽  
Bo-hou Xia ◽  
Zhi-min Zhang ◽  
Chun Li ◽  
...  
Keyword(s):  
Amino Acid ◽  
Glucose Metabolism ◽  
Liver Injury ◽  
Gas Chromatography Mass Spectrometry ◽  
Hexadecanoic Acid ◽  
Hydroxybutyric Acid ◽  
Polygonum Multiflorum ◽  
Rat Serum ◽  
Metabolic Biomarkers ◽  
Endogenous Metabolites

Abstract Background The idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury. Methods Serum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Gas chromatography/mass spectrometry (GC-MS) was performed to identify changes in metabolic biomarkers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was applied to determine group clustering trends and differential metabolites. Results The results for the liver index, the liver function index and liver pathology showed that Polygonum multiflorum ethanol extract (PME), 50% ethanol elution fractions and tetrahydroxystilbene glucoside (TSG) from PME can induce idiosyncratic hepatotoxicity. TSG was the main idiosyncratically hepatotoxic component. Forty endogenous metabolites were identified in the rat liver. Six biomarkers, including lower levels of L-valine and higher levels of 3-hydroxybutyric acid, hexadecanoic acid, ribose, phosphoric acid and oxalic acid, were related to PM-induced liver injury. These differential biomarkers led to disruptions in amino acid, fatty acid, oxalate, energy and glucose metabolism. A total of 32 types of endogenous metabolites were identified in rat serum. Ten biomarkers were related to the liver injury induced by TSG, including lower levels of L-valine and L-proline and higher levels of urea, caproic acid, DL-malic acid, D-mannose, 3-hydroxybutyric acid, D-galactose, octadecane and hexadecanoic acid. These differential biomarkers led to disruptions in amino acid, glucose and fat metabolism. The mechanism of idiosyncratic hepatotoxicity in PM involves TSG-induced disruptions in amino acid metabolism, lipid metabolism, energy metabolism and glucose metabolism. Conclusions These findings reflect the material basis and metabolic mechanism of idiosyncratic PM hepatotoxicity.

scholarly journals A GC-MS-based Metabolomic Strategy to Investigate the Protective Effects of Mulberry Polysaccharide on CCl4-induced Acute Liver Injury in Mice

2021 ◽  
Author(s):  
Xiaofen Ma ◽  
Jian Yang ◽  
Subinur Baker ◽  
Zhen Li ◽  
Xin Li ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Gas Chromatography Mass Spectrometry ◽  
Protective Effects ◽  
Protective Mechanisms ◽  
Tissue Sections ◽  
Hematoxylin And Eosin ◽  
Endogenous Metabolites ◽  
Mulberry Tree ◽  
Southern Xinjiang

Abstract BackgroundMulberry (Morus alba) fruits of the woody mulberry tree (family: Moraceae Morus) is a type of mulberry fruit grown in the southern Xinjiang region,which polysaccharides have antioxidant and liver protective effects.This article further preliminary study on the protective effects of mulberry polysaccharide (MP) on liver.MethodsA detection kit was used to assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver malondialdehyde (MDA), superoxide dismutase (SOD) and other indicators. Liver tissue sections were stained with hematoxylin and eosin (H&E) and observed under a microscope. The entire endogenous metabolite profiling was acquired via metabolomics strategy using gas chromatography-mass spectrometry (GC-MS) to assess the underlying protective mechanisms of MPs. ResultsResults indicated that MPs exerted a hepatoprotective effect on acute liver injury by decreasing serum ALT and AST levels, hepatic MDA, and restored hepatic SOD glutathione peroxidase (GSH-Px) activities. A total of 33 possible endogenous metabolites associated with lipid, glucose, and energy metabolism including amino acids, sugars, and fatty acids, were found.ConclusionsThe results of the present study provide a reference for elucidating the protective mechanisms of MPs against acute liver injury.

scholarly journals Metabolomics of a cell line-derived xenograft model reveals circulating metabolic signatures for malignant mesothelioma

PeerJ ◽  
2022 ◽  
Vol 10 ◽  
pp. e12568
Author(s):  
Yun Gao ◽  
Ziyi Dai ◽  
Chenxi Yang ◽  
Ding Wang ◽  
Zhenying Guo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Line ◽  
Malignant Mesothelioma ◽  
Roc Analysis ◽  
Xenograft Model ◽  
Mass Spectrometry Analysis ◽  
Gas Chromatography Mass Spectrometry ◽  
Plasma Metabolites ◽  
P Value ◽  
Metabolic Biomarkers

Background Malignant mesothelioma (MM) is a rare and highly aggressive cancer. Despite advances in multidisciplinary treatments for cancer, the prognosis for MM remains poor with no effective diagnostic biomarkers currently available. The aim of this study was to identify plasma metabolic biomarkers for better MM diagnosis and prognosis by use of a MM cell line-derived xenograft (CDX) model. Methods The MM CDX model was confirmed by hematoxylin and eosin staining and immunohistochemistry. Twenty female nude mice were randomly divided into two groups, 10 for the MM CDX model and 10 controls. Plasma samples were collected two weeks after tumor cell implantation. Gas chromatography-mass spectrometry analysis was conducted. Both univariate and multivariate statistics were used to select potential metabolic biomarkers. Hierarchical clustering analysis, metabolic pathway analysis, and receiver operating characteristic (ROC) analysis were performed. Additionally, bioinformatics analysis was used to investigate differential genes between tumor and normal tissues, and survival-associated genes. Results The MM CDX model was successfully established. With VIP > 1.0 and P-value < 0.05, a total of 23 differential metabolites were annotated, in which isoleucine, 5-dihydrocortisol, and indole-3-acetamide had the highest diagnostic values based on ROC analysis. These were mainly enriched in pathways for starch and sucrose metabolism, pentose and glucuronate interconversions, galactose metabolism, steroid hormone biosynthesis, as well as phenylalanine, tyrosine and tryptophan biosynthesis. Further, down-regulation was observed for amino acids, especially isoleucine, which is consistent with up-regulation of amino acid transporter genes SLC7A5 and SLC1A3 in MM. Overall survival was also negatively associated with SLC1A5, SLC7A5, and SLC1A3. Conclusion We found several altered plasma metabolites in the MM CDX model. The importance of specific metabolic pathways, for example amino acid metabolism, is herein highlighted, although further investigation is warranted.

Alterations of Glucose Metabolism in Viral and Toxic Liver Injury

1964 ◽  
Vol 46 (4) ◽  
pp. 424-433 ◽  
Author(s):  
Kurt J. Isselbacher ◽  
Wallace A. Jones
Keyword(s):  
Glucose Metabolism ◽  
Liver Injury ◽  
Toxic Liver Injury

scholarly journals Intestinal Protein Supply Alters Amino Acid, but Not Glucose, Metabolism by the Sheep Gastrointestinal Tract

2006 ◽  
Vol 136 (5) ◽  
pp. 1261-1269 ◽  
Author(s):  
Samer W. El-Kadi ◽  
Ransom L. Baldwin ◽  
Nishanth E. Sunny ◽  
Sandra L. Owens ◽  
Brian J. Bequette
Keyword(s):  
Amino Acid ◽  
Gastrointestinal Tract ◽  
Glucose Metabolism ◽  
Intestinal Protein ◽  
Protein Supply

Idiosyncratic drug-induced liver injury linked to Polygonum multiflorum: A case study by pharmacognosy

2017 ◽  
Vol 23 (8) ◽  
pp. 625-630 ◽  
Author(s):  
Chun-yu Li ◽  
Qin He ◽  
Dan Gao ◽  
Rui-yu Li ◽  
Yun Zhu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Polygonum Multiflorum ◽  
Drug Induced ◽  
Drug Induced Liver Injury

scholarly journals Sandalwood, an Indian medicinal plant attenuates the microbial growth and influence up/down regulation of the metabolites

2021 ◽  
Author(s):  
Romana Parveen ◽  
Tooba Naz Shamsi ◽  
Sadaf Fatima
Keyword(s):  
Methyl Ester ◽  
Octadecenoic Acid ◽  
Acid Methyl Ester ◽  
Gas Chromatography Mass Spectrometry ◽  
Hexadecanoic Acid ◽  
Trimethylsilyl Ester ◽  
E Coli ◽  
Acid Methyl ◽  
Soxhlet Apparatus ◽  
Antibacterial Assay

AbstractThe methanolic extract of sandalwood (SwME) was prepared by soxhlet apparatus and the antibacterial assay was performed. Further, the metabolite profiling of SwME and lysates of E. coli and E. coli grown in the presence of SwME was generated. SwME showed maximum inhibition against E. coli (MTCC 443) i.e. 82.71%, and minimal against B. subtilis (MTCC 736) i.e. 26.82%. The metabolome profiles of E. coli and SwME were generated using gas chromatography-mass spectrometry (GC-MS) technique. Comparative studies were done to understand to what extent metabolite modifications differ between SwME, E. coli lysate and the E. coli strain grown in presence of extract. Result revealed 23 peaks with major compounds present in E. coli were 9-Octadecenoic Acid (Z)-, Methyl Ester (26.85%), Hexadecanoic Acid, methyl ester (20.5%) and Hexadecanoic acid, trimethylsilyl ester (15.79%). When E. coli was grown in the presence of SwME, GC-MS analysis showed 25 peaks with major compounds such as 9-Octadecenoic Acid, Methyl Ester (21.97%), Hexadecanoic Acid, Methyl Ester (17.03%), and Hexadecanoic Acid, Trimethylsilyl Ester (14.96%). Correlating the metabolic profiles with the changes occurring is essential to progression their comprehension and in the development of new approaches to identify the metabolomics regulation in E. coli in response to SwME.

scholarly journals Lipidomics Analysis Indicates Disturbed Hepatocellular Lipid Metabolism in Reynoutria multiflora-Induced Idiosyncratic Liver Injury

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaofang Wu ◽  
Yating Zhang ◽  
Jiaqi Qiu ◽  
Ya Xu ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Injury ◽  
Rat Liver ◽  
High Performance ◽  
Phospholipid Metabolism ◽  
Polygonum Multiflorum ◽  
Drug Induced ◽  
Metabolic Characteristics ◽  
Lipid Biomarker ◽  
Q Exactive

The root of Reynoutria multiflora (Thunb.) Moldenke (syn.: Polygonum multiflorum Thunb., HSW) is a distinguished herb that has been popularly used in traditional Chinese medicine (TCM). Evidence of its potential side effect on liver injury has accumulated and received much attention. The objective of this study was to profile the metabolic characteristics of lipids in injured liver of rats induced by HSW and to find out potential lipid biomarkers of toxic consequence. A lipopolysaccharide (LPS)-induced rat model of idiosyncratic drug-induced liver injury (IDILI) was constructed and evident liver injury caused by HSW was confirmed based on the combination of biochemical, morphological, and functional tests. A lipidomics method was developed for the first time to investigate the alteration of lipid metabolism in HSW-induced IDILI rat liver by using ultra-high-performance liquid chromatography/Q-exactive Orbitrap mass spectrometry coupled with multivariate analysis. A total of 202 characterized lipids, including phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), sphingomyelin (SM), phosphatidylinositol (PI), lysophosphatidylinositol (LPI), phosphatidylserine (PS), phosphoglycerols (PG), and ceramide (Cer), were compared among groups of LPS and LPS + HSW. A total of 14 out 26 LPC, 22 out of 47 PC, 19 out of 29 LPE, 16 out of 36 PE, and 10 out of 15 PI species were increased in HSW-treated rat liver, which indicated that HSW may cause liver damage via interfering the phospholipid metabolism. The present work may assist lipid biomarker development of HSW-induced DILI and it also provide new insights into the relationships between phospholipid perturbation and herbal-induced idiosyncratic DILI.

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