Pattern Recognition Analysis for Hepatotoxicity Induced by Acetaminophen Using Plasma and Urinary H-1 NMR-Based Metabolomics in Humans

Title
Pattern Recognition Analysis for Hepatotoxicity Induced by Acetaminophen Using Plasma and Urinary H-1 NMR-Based Metabolomics in Humans
Author(s)
임미선Kim JW[Kim JW]Sung Ha Ryu[Sung Ha Ryu]Siwon Kim[Siwon Kim]Hae Won Lee[Hae Won Lee]Sook Jin Seong[Sook Jin Seong]Suhkmann Kim[Suhkmann Kim]Young-Ran Yoon[Young-Ran Yoon]Kyu-Bong Kim[Kyu-Bong Kim]
Keywords
INDUCED LIVER-INJURY; OXIDATIVE-PHOSPHORYLATION; CARBON-TETRACHLORIDE; GLUTAMINE-SYNTHETASE; METABONOMIC APPROACH; UNITED-STATES; SPECTRAL DATA; RATS; FAILURE; SPECTROSCOPY
Issue Date
201312
Publisher
AMER CHEMICAL SOC
Citation
ANALYTICAL CHEMISTRY, v.85, no.23, pp.11326 - 11334
Abstract
Drug-induced liver injury (DILI) is currently an increasingly relevant health issue. However, available biomarkers do not reliably detect or quantify DILL risk. Therefore, the purpose of this study was to comparatively evaluate plasma and urinary biomarkers obtained from humans treated with acetaminophen (APAP) using a metabolomics approach and a proton nuclear magnetic resonance (NMR) platform. APAP (3 g/day, two 500 mg tablets every 8 h) was administered to 20 healthy Korean males (age, 20-29 years) for 7 days. Urine was collected daily before and during dosing and 6 days after the final dose. NMR spectra of these urine samples were analyzed using principal component analysis (PCA) and partial least-squares-discrimination analysis. Although the activities of aspartate aminotransferase and lactate dehydrogenase were significantly increased 7 days post-APAP treatment, serum biochemical parameters of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, gamma-glutamyl transpeptidase, and lactate dehydrogenase were within normal range of hepatic function. However, urine and plasma H-1 NMR spectroscopy revealed different clustering between predosing and after APAP treatment for global metabolomic profiling through PCA. Urinary endogenous metabolites of trimethylamine-N-oxide, citrate, 3-chlorotyrosine, phenylalanine, glycine, hippurate, and glutarate as well as plasma endogenous metabolites such as lactate, glucose, 3-hydroxyisovalerate, isoleucine, acetylglycine, acetone, acetate, glutamine, ethanol, and isobutyrate responded significantly to APAP dosing in humans. Urinary and plasma endogenous metabolites were more sensitive than serum biochemical parameters. These results might be applied to predict or screen potential hepatotoxicity caused by other drugs using urinary and plasma H-1 NMR analyses.
URI
http://hdl.handle.net/YU.REPOSITORY/28187http://dx.doi.org/10.1021/ac402390q
ISSN
0003-2700
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약학대학 > 약학부 > Articles
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