H-1 NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease
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, a...
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my.utm.555412017-02-15T04:41:25Z http://eprints.utm.my/id/eprint/55541/ H-1 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 TP Chemical technology 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 (HNMR)-H-1 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 (a-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, a-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 Article PeerReviewed Xu, Jingjing and Jiang, Huaizhou and Li, Jinquan and Cheng, Kian-Kai and Dong, Jiyang and Chen, Zhong (2015) H-1 NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease. Plos One, 10 (4). ISSN 1932-6203 http://dx.doi.org/10.1371/journal.pone.0119654 DOI:10.1371/journal.pone.0119654 |
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TP Chemical technology Xu, Jingjing Jiang, Huaizhou Li, Jinquan Cheng, Kian-Kai Dong, Jiyang Chen, Zhong H-1 NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease |
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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 (HNMR)-H-1 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 (a-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, a-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 |
Article |
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 |
title |
H-1 NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease |
title_short |
H-1 NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease |
title_full |
H-1 NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease |
title_fullStr |
H-1 NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease |
title_full_unstemmed |
H-1 NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease |
title_sort |
h-1 nmr-based metabolomics investigation of copper-laden rat: a model of wilson's disease |
publisher |
Public Library of Science |
publishDate |
2015 |
url |
http://eprints.utm.my/id/eprint/55541/ http://dx.doi.org/10.1371/journal.pone.0119654 |
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1643653828811161600 |
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13.160551 |