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Metabolic profiling reveals the protective effect of diammonium glycyrrhizinate on acute hepatic injury induced by carbon tetrachloride

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Abstract

Diammonium glycyrrhizinate (DG), a constitutent of Glycyrrhiza uralensis, has a protective effect on hepatic injury, hepatisis and cirrhosis. To date, the mechanism has been poorly understood, especially at the metabolic level. A metabolomic profiling study was performed to characterize the carbon tetrachloride (CCl4) induced global metabolic alteration and the protective effects of DG in Sprague-Dawley rats. Urinary and hepatic tissue metabolic profiling revealed that CCl4 perturbed the amino acid metabolism (alanine, glycine, leucine), tricarboxylic acid cycle (citrate), lipid metabolism (unsaturated fatty acids) and gut microbiota related metabolites. Our results also indicated that DG was able to attenuate CCl4 perturbed metabolic pathways and ameliorated biochemical markers of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Total cholesterol (TCHO). This global metabolomic approach also revealed full metabolic recovery takes longer than apparent and conventional histological and biochemical markers.

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Abbreviations

DG:

Diammonium glycyrrhizinate

NC:

Normal control

TCHO:

Total cholesterol

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

MDA:

Malondiadehyde

SOD:

Superoxide dismutase

GSH-px:

Glutathion peroxidase

ECF:

Ethylchloroformate

PCA:

Principal component analysis

PLS-DA:

Partial least squares discriminant analysis

PC:

Principal component

GSH:

Reduced glutathione

GSSG:

Oxidized glutathione

DOPAC:

3,4-Dihydroxy-phenylacetate

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Acknowledgments

This work was financially supported by the National Basic Research Program of China (2007CB914700), the National Science and Technology Major Project (2009ZX10005-020) and the National Natural Science Foundation of China Grant 30901997, 20775048 and the International Collaborative Project of Chinese Ministry of Science and Technology (2006DFA02700).

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Authors and Affiliations

  1. Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China

    Xiaoyan Wang, Jingchao Lin & Tianlu Chen

  2. Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Mingmei Zhou

  3. David H. Murdock Research Institute, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA

    Mingming Su & Wei Jia

  4. Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC, 28081, USA

    Wei Jia

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  1. Xiaoyan Wang
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  2. Jingchao Lin
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  3. Tianlu Chen
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  4. Mingmei Zhou
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  5. Mingming Su
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  6. Wei Jia
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Correspondence to Wei Jia.

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Wang, X., Lin, J., Chen, T. et al. Metabolic profiling reveals the protective effect of diammonium glycyrrhizinate on acute hepatic injury induced by carbon tetrachloride. Metabolomics 7, 226–236 (2011). https://doi.org/10.1007/s11306-010-0244-5

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