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A GC–MS-based untargeted metabolomics approach for comprehensive metabolic profiling of vancomycin-induced toxicity in mice

BACKGROUND: Vancomycin is a glycopeptide antibiotic that is commonly used for severe drug-resistant infections treatment. Application of vancomycin frequently leads to severe ototoxicity, hepatotoxicity, and nephrotoxicity; however, the comprehensive metabolic analysis of vancomycin-induced toxicity...

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Autores principales: Cui, Changmeng, Zhu, Li, Wang, Qian, Liu, Ruijuan, Xie, Dadi, Guo, Yujin, Yu, Dingyi, Wang, Changshui, Chen, Dan, Jiang, Pei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287194/
https://www.ncbi.nlm.nih.gov/pubmed/35855991
http://dx.doi.org/10.1016/j.heliyon.2022.e09869
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author Cui, Changmeng
Zhu, Li
Wang, Qian
Liu, Ruijuan
Xie, Dadi
Guo, Yujin
Yu, Dingyi
Wang, Changshui
Chen, Dan
Jiang, Pei
author_facet Cui, Changmeng
Zhu, Li
Wang, Qian
Liu, Ruijuan
Xie, Dadi
Guo, Yujin
Yu, Dingyi
Wang, Changshui
Chen, Dan
Jiang, Pei
author_sort Cui, Changmeng
collection PubMed
description BACKGROUND: Vancomycin is a glycopeptide antibiotic that is commonly used for severe drug-resistant infections treatment. Application of vancomycin frequently leads to severe ototoxicity, hepatotoxicity, and nephrotoxicity; however, the comprehensive metabolic analysis of vancomycin-induced toxicity is lacking. PURPOSE: This study attempted to investigate the metabolic changes after vancomycin administration in mice. METHODS: Experimental mice (n = 9) received continuous intraperitoneal injection of vancomycin (400 mg/kg) every day for 7 days, and mice in control group (n = 9) were treated with the same amount of normal saline. Pathological changes of the kidney were examined using haematoxylin and eosin (HE) staining. A gas chromatography-mass spectrometry (GC-MS) approach was used to identify discriminant metabolites in serum and various organs including the heart, liver, kidney, spleen, cerebral cortex, hippocampus, inner ear, lung, and intestine. The potential metabolites were identified using orthogonal partial least squares discrimination analysis (OPLS-DA). Subsequently, the MetaboAnalyst 5.0 (http://www.metaboanalyst.ca) and Kyoto Encyclopedia of Genes and Genomes database (KEGG, http://www.kegg.jp) were employed to depict the metabolic pathways. RESULTS: Compared with the control group, the vancomycin induced 13, 17, 27, 22, 16, 10, 17, 11, 10, and 7 differential metabolites in the serum, liver, kidney, heart, cerebral cortex, lung, spleen, intestine, hippocampus, and inner ear, respectively. Further pathway analyses identified that amino acids metabolism, fatty acids biosynthesis, energy metabolism, and lipid metabolism were disrupted after VCM exposure. CONCLUSION: Vancomycin affects the metabolism in various organs in mice, which provides new insights for identification of vancomycin-induced toxicity, and facilitate to better understanding of the metabolic pathogenesis of vancomycin.
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spelling pubmed-92871942022-07-17 A GC–MS-based untargeted metabolomics approach for comprehensive metabolic profiling of vancomycin-induced toxicity in mice Cui, Changmeng Zhu, Li Wang, Qian Liu, Ruijuan Xie, Dadi Guo, Yujin Yu, Dingyi Wang, Changshui Chen, Dan Jiang, Pei Heliyon Research Article BACKGROUND: Vancomycin is a glycopeptide antibiotic that is commonly used for severe drug-resistant infections treatment. Application of vancomycin frequently leads to severe ototoxicity, hepatotoxicity, and nephrotoxicity; however, the comprehensive metabolic analysis of vancomycin-induced toxicity is lacking. PURPOSE: This study attempted to investigate the metabolic changes after vancomycin administration in mice. METHODS: Experimental mice (n = 9) received continuous intraperitoneal injection of vancomycin (400 mg/kg) every day for 7 days, and mice in control group (n = 9) were treated with the same amount of normal saline. Pathological changes of the kidney were examined using haematoxylin and eosin (HE) staining. A gas chromatography-mass spectrometry (GC-MS) approach was used to identify discriminant metabolites in serum and various organs including the heart, liver, kidney, spleen, cerebral cortex, hippocampus, inner ear, lung, and intestine. The potential metabolites were identified using orthogonal partial least squares discrimination analysis (OPLS-DA). Subsequently, the MetaboAnalyst 5.0 (http://www.metaboanalyst.ca) and Kyoto Encyclopedia of Genes and Genomes database (KEGG, http://www.kegg.jp) were employed to depict the metabolic pathways. RESULTS: Compared with the control group, the vancomycin induced 13, 17, 27, 22, 16, 10, 17, 11, 10, and 7 differential metabolites in the serum, liver, kidney, heart, cerebral cortex, lung, spleen, intestine, hippocampus, and inner ear, respectively. Further pathway analyses identified that amino acids metabolism, fatty acids biosynthesis, energy metabolism, and lipid metabolism were disrupted after VCM exposure. CONCLUSION: Vancomycin affects the metabolism in various organs in mice, which provides new insights for identification of vancomycin-induced toxicity, and facilitate to better understanding of the metabolic pathogenesis of vancomycin. Elsevier 2022-07-06 /pmc/articles/PMC9287194/ /pubmed/35855991 http://dx.doi.org/10.1016/j.heliyon.2022.e09869 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Cui, Changmeng
Zhu, Li
Wang, Qian
Liu, Ruijuan
Xie, Dadi
Guo, Yujin
Yu, Dingyi
Wang, Changshui
Chen, Dan
Jiang, Pei
A GC–MS-based untargeted metabolomics approach for comprehensive metabolic profiling of vancomycin-induced toxicity in mice
title A GC–MS-based untargeted metabolomics approach for comprehensive metabolic profiling of vancomycin-induced toxicity in mice
title_full A GC–MS-based untargeted metabolomics approach for comprehensive metabolic profiling of vancomycin-induced toxicity in mice
title_fullStr A GC–MS-based untargeted metabolomics approach for comprehensive metabolic profiling of vancomycin-induced toxicity in mice
title_full_unstemmed A GC–MS-based untargeted metabolomics approach for comprehensive metabolic profiling of vancomycin-induced toxicity in mice
title_short A GC–MS-based untargeted metabolomics approach for comprehensive metabolic profiling of vancomycin-induced toxicity in mice
title_sort gc–ms-based untargeted metabolomics approach for comprehensive metabolic profiling of vancomycin-induced toxicity in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287194/
https://www.ncbi.nlm.nih.gov/pubmed/35855991
http://dx.doi.org/10.1016/j.heliyon.2022.e09869
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