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(1)H NMR-Based Metabolomics Investigation of Copper-Laden Rat: A Model of Wilson’s Disease
BACKGROUND AND PURPOSE: Wilson’s disease (WD), also known as hepatoleticular degeneration (HLD), is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical mani...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388371/ https://www.ncbi.nlm.nih.gov/pubmed/25849323 http://dx.doi.org/10.1371/journal.pone.0119654 |
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author | Xu, Jingjing Jiang, Huaizhou Li, Jinquan Cheng, Kian-Kai Dong, Jiyang Chen, Zhong |
author_facet | Xu, Jingjing Jiang, Huaizhou Li, Jinquan Cheng, Kian-Kai Dong, Jiyang Chen, Zhong |
author_sort | Xu, Jingjing |
collection | PubMed |
description | BACKGROUND AND PURPOSE: Wilson’s disease (WD), also known as hepatoleticular degeneration (HLD), is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of ‘decoppering’ process, penicillamine (PA) was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established. MATERIALS AND METHODS: A combination of (1)HNMR spectroscopy and multivariate statistical analysis was applied to examine the metabolic profiles of the urine and blood serum samples collected from the copper-laden rat model of WD with PA treatment. RESULTS: Copper accumulation in the copper-laden rats is associated with increased lactate, creatinine, valine and leucine, as well as decreased levels of glucose and taurine in the blood serum. There were also significant changes in p-hydroxyphenylacetate (p-HPA), creatinine, alpha-ketoglutarate (α-KG), dimethylamine, N-acetylglutamate (NAG), N-acetylglycoprotein (NAC) in the urine of these rats. Notably, the changes in p-HPA, glucose, lactate, taurine, valine, leucine, and NAG were found reversed following PA treatment. Nevertheless, there were no changes for dimethylamine, α-KG, and NAC as a result of the treatment. Compared with the controls, the concentrations of hippurate, formate, alanine, and lactate were changed when PA was applied and this is probably due to its side effect. A tool named SMPDB (Small Molecule Pathway Database) is introduced to identify the metabolic pathway influenced by the copper-laden diet. CONCLUSION: The study has shown the potential application of NMR-based metabolomic analysis in providing further insights into the molecular mechanism underlying disorder due to WD. |
format | Online Article Text |
id | pubmed-4388371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43883712015-04-21 (1)H NMR-Based Metabolomics Investigation of Copper-Laden Rat: A Model of Wilson’s Disease Xu, Jingjing Jiang, Huaizhou Li, Jinquan Cheng, Kian-Kai Dong, Jiyang Chen, Zhong PLoS One Research Article BACKGROUND AND PURPOSE: Wilson’s disease (WD), also known as hepatoleticular degeneration (HLD), is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of ‘decoppering’ process, penicillamine (PA) was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established. MATERIALS AND METHODS: A combination of (1)HNMR spectroscopy and multivariate statistical analysis was applied to examine the metabolic profiles of the urine and blood serum samples collected from the copper-laden rat model of WD with PA treatment. RESULTS: Copper accumulation in the copper-laden rats is associated with increased lactate, creatinine, valine and leucine, as well as decreased levels of glucose and taurine in the blood serum. There were also significant changes in p-hydroxyphenylacetate (p-HPA), creatinine, alpha-ketoglutarate (α-KG), dimethylamine, N-acetylglutamate (NAG), N-acetylglycoprotein (NAC) in the urine of these rats. Notably, the changes in p-HPA, glucose, lactate, taurine, valine, leucine, and NAG were found reversed following PA treatment. Nevertheless, there were no changes for dimethylamine, α-KG, and NAC as a result of the treatment. Compared with the controls, the concentrations of hippurate, formate, alanine, and lactate were changed when PA was applied and this is probably due to its side effect. A tool named SMPDB (Small Molecule Pathway Database) is introduced to identify the metabolic pathway influenced by the copper-laden diet. CONCLUSION: The study has shown the potential application of NMR-based metabolomic analysis in providing further insights into the molecular mechanism underlying disorder due to WD. Public Library of Science 2015-04-07 /pmc/articles/PMC4388371/ /pubmed/25849323 http://dx.doi.org/10.1371/journal.pone.0119654 Text en © 2015 Xu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Xu, Jingjing Jiang, Huaizhou Li, Jinquan Cheng, Kian-Kai Dong, Jiyang Chen, Zhong (1)H NMR-Based Metabolomics Investigation of Copper-Laden Rat: A Model of Wilson’s Disease |
title |
(1)H NMR-Based Metabolomics Investigation of Copper-Laden Rat: A Model of Wilson’s Disease |
title_full |
(1)H NMR-Based Metabolomics Investigation of Copper-Laden Rat: A Model of Wilson’s Disease |
title_fullStr |
(1)H NMR-Based Metabolomics Investigation of Copper-Laden Rat: A Model of Wilson’s Disease |
title_full_unstemmed |
(1)H NMR-Based Metabolomics Investigation of Copper-Laden Rat: A Model of Wilson’s Disease |
title_short |
(1)H NMR-Based Metabolomics Investigation of Copper-Laden Rat: A Model of Wilson’s Disease |
title_sort | (1)h nmr-based metabolomics investigation of copper-laden rat: a model of wilson’s disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388371/ https://www.ncbi.nlm.nih.gov/pubmed/25849323 http://dx.doi.org/10.1371/journal.pone.0119654 |
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