Changes of Lipopolysaccharide-Induced Acute Kidney and Liver Injuries in Rats Based on Metabolomics Analysis

Huan Gao,1 Tao Yang,2 Xuan Chen,3 Yanqing Song1 1Department of Pharmacy, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 2Houde Food Co., Ltd, Liaoyuan, 136200, People’s Republic of China; 3Department of Neurosurgery, The First Hospital of J...

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Autores principales:	Gao H, Yang T, Chen X, Song Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	untargeted metabolomics lps acute kidney injury acute liver injury amino acid metabolism Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2f2927f0ee4c4876acaf5dd7252ace43
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spelling	oai:doaj.org-article:2f2927f0ee4c4876acaf5dd7252ace432021-12-02T15:33:24ZChanges of Lipopolysaccharide-Induced Acute Kidney and Liver Injuries in Rats Based on Metabolomics Analysis1178-7031https://doaj.org/article/2f2927f0ee4c4876acaf5dd7252ace432021-05-01T00:00:00Zhttps://www.dovepress.com/changes-of-lipopolysaccharide-induced-acute-kidney-and-liver-injuries--peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Huan Gao,1 Tao Yang,2 Xuan Chen,3 Yanqing Song1 1Department of Pharmacy, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 2Houde Food Co., Ltd, Liaoyuan, 136200, People’s Republic of China; 3Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Yanqing SongDepartment of Pharmacy, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of ChinaTel +86 431 88782482Email songyanq@jlu.edu.cnBackground: The bacterial endotoxin lipopolysaccharide (LPS) was the classic inducer to establish many inflammatory disease models, especially multiple organ injury. Evidences indicated that the mechanism that causes inflammation response is not just related to cytokine release. The main aim of this study was to better elucidate the possible links between metabolic changes and the pathogenesis of LPS-induced acute liver and kidney in order to understand the mechanisms and screening therapeutic targets for developing early diagnostic strategies and treatments.Methods: An experimental rat model was established by intraperitoneal injection of 10 mg/kg LPS. An untargeted metabolomics analysis of the serum in the LPS and control groups was carried out using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QTOF-MS). LPS-induced pathological damage in the lungs, liver, kidneys, and colon was observed, along with changes in biochemical indexes, indicating that there was a severe inflammatory response in many organs after administration of LPS for 8 h. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) showed distinct separation in the serum metabolite profiles between the LPS and control groups, indicating significant changes in endogenous metabolites.Results: The untargeted metabolomics analysis showed that there were 127 significantly different serum metabolites and 53 altered pathways after LPS administration, including pathways related to the metabolism of D-glutamine and D-glutamate, taurine and hypotaurine, beta-alanine, glutathione, and butanoate, which are involved in the inflammatory response, oxidative stress, and amino acid metabolism.Conclusion: The study suggested that LPS-induced acute liver and kidney injury mainly involves inflammatory response, oxidative stress, and protein synthesis, finally causing multi-organ damage. Correcting the disturbances to the metabolites and metabolic pathways may help to prevent and/or treat LPS-induced acute liver and kidney damage.Keywords: untargeted metabolomics, LPS, acute kidney injury, acute liver injury, amino acid metabolismGao HYang TChen XSong YDove Medical Pressarticleuntargeted metabolomicslpsacute kidney injuryacute liver injuryamino acid metabolismPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 1807-1825 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	untargeted metabolomics lps acute kidney injury acute liver injury amino acid metabolism Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	untargeted metabolomics lps acute kidney injury acute liver injury amino acid metabolism Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Gao H Yang T Chen X Song Y Changes of Lipopolysaccharide-Induced Acute Kidney and Liver Injuries in Rats Based on Metabolomics Analysis
description	Huan Gao,1 Tao Yang,2 Xuan Chen,3 Yanqing Song1 1Department of Pharmacy, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 2Houde Food Co., Ltd, Liaoyuan, 136200, People’s Republic of China; 3Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Yanqing SongDepartment of Pharmacy, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of ChinaTel +86 431 88782482Email songyanq@jlu.edu.cnBackground: The bacterial endotoxin lipopolysaccharide (LPS) was the classic inducer to establish many inflammatory disease models, especially multiple organ injury. Evidences indicated that the mechanism that causes inflammation response is not just related to cytokine release. The main aim of this study was to better elucidate the possible links between metabolic changes and the pathogenesis of LPS-induced acute liver and kidney in order to understand the mechanisms and screening therapeutic targets for developing early diagnostic strategies and treatments.Methods: An experimental rat model was established by intraperitoneal injection of 10 mg/kg LPS. An untargeted metabolomics analysis of the serum in the LPS and control groups was carried out using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QTOF-MS). LPS-induced pathological damage in the lungs, liver, kidneys, and colon was observed, along with changes in biochemical indexes, indicating that there was a severe inflammatory response in many organs after administration of LPS for 8 h. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) showed distinct separation in the serum metabolite profiles between the LPS and control groups, indicating significant changes in endogenous metabolites.Results: The untargeted metabolomics analysis showed that there were 127 significantly different serum metabolites and 53 altered pathways after LPS administration, including pathways related to the metabolism of D-glutamine and D-glutamate, taurine and hypotaurine, beta-alanine, glutathione, and butanoate, which are involved in the inflammatory response, oxidative stress, and amino acid metabolism.Conclusion: The study suggested that LPS-induced acute liver and kidney injury mainly involves inflammatory response, oxidative stress, and protein synthesis, finally causing multi-organ damage. Correcting the disturbances to the metabolites and metabolic pathways may help to prevent and/or treat LPS-induced acute liver and kidney damage.Keywords: untargeted metabolomics, LPS, acute kidney injury, acute liver injury, amino acid metabolism
format	article
author	Gao H Yang T Chen X Song Y
author_facet	Gao H Yang T Chen X Song Y
author_sort	Gao H
title	Changes of Lipopolysaccharide-Induced Acute Kidney and Liver Injuries in Rats Based on Metabolomics Analysis
title_short	Changes of Lipopolysaccharide-Induced Acute Kidney and Liver Injuries in Rats Based on Metabolomics Analysis
title_full	Changes of Lipopolysaccharide-Induced Acute Kidney and Liver Injuries in Rats Based on Metabolomics Analysis
title_fullStr	Changes of Lipopolysaccharide-Induced Acute Kidney and Liver Injuries in Rats Based on Metabolomics Analysis
title_full_unstemmed	Changes of Lipopolysaccharide-Induced Acute Kidney and Liver Injuries in Rats Based on Metabolomics Analysis
title_sort	changes of lipopolysaccharide-induced acute kidney and liver injuries in rats based on metabolomics analysis
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/2f2927f0ee4c4876acaf5dd7252ace43
work_keys_str_mv	AT gaoh changesoflipopolysaccharideinducedacutekidneyandliverinjuriesinratsbasedonmetabolomicsanalysis AT yangt changesoflipopolysaccharideinducedacutekidneyandliverinjuriesinratsbasedonmetabolomicsanalysis AT chenx changesoflipopolysaccharideinducedacutekidneyandliverinjuriesinratsbasedonmetabolomicsanalysis AT songy changesoflipopolysaccharideinducedacutekidneyandliverinjuriesinratsbasedonmetabolomicsanalysis
_version_	1718387073548812288

Changes of Lipopolysaccharide-Induced Acute Kidney and Liver Injuries in Rats Based on Metabolomics Analysis

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