Journal
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Volume 52, Issue 1, Pages 136-141Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jpba.2009.12.026
Keywords
Huang-yao-zi; Metabonomics; H-1 NMR; Liver toxicity; Biomarker
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Funding
- National Natural Science Foundation of China [20672143]
- Integrated drug R D Platform [2009ZX09301-002]
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Urinary metabolic perturbations associated with liver toxicity induced by Huang-yao-zi (root of Dioscorea bulifera L.) were studied using nuclear magnetic resonance spectroscopy (H-1 NMR) to determine the correlations between metabonomic profiling and histopathologic/biochemical observations and to discover biomarkers for liver toxicity. Huang-yao-zi with a maximal tolerance dose (MTD) was given to male Sprague-Dawley rats for 72 h followed by metabonomic analysis of urine samples collected at 24 and 72 h. The results revealed that the levels of taurine, creatine, betaine, dimethylglycine (DMG), acetate, glycine were elevated, whereas, the levels of succinate, 2-oxoglutarate, citrate, hippurate and urea were reduced. Partial least square (PLS)-discrimination analysis (DA) of NMR spectra revealed two apparent clusters between control groups and treatment groups, indicating metabolic changes observed in urine samples in response to Huang-yao-zi treatment. In addition, mechanism associated with oxidative injury of hepatic mitochondria was investigated. These results indicated that H-1 NMR-based metabonomics analysis in urine samples may be useful for predicting hepatotoxicity induced by Huang-yao-zi. (C) 2009 Elsevier B.V. All rights reserved.
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