skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease

Abstract

Metabolomic evaluation of urine and liver was conducted to assess the biochemical changes that occur as a result of alcohol-induced liver injury. Male C57BL/6J mice were fed an isocaloric control- or alcohol-containing liquid diet with 35% of calories from corn oil, 18% protein and 47% carbohydrate/alcohol for up to 36 days ad libitum. Alcohol treatment was initiated at 7 g/kg/day and gradually reached a final dose of 21 g/kg/day. Urine samples were collected at 22, 30 and 36 days and, in additional treatment groups, liver and serum samples were harvested at 28 days. Steatohepatitis was induced in the alcohol-fed group since a 5-fold increase in serum alanine aminotransferase activity, a 6-fold increase in liver injury score (necrosis, inflammation and steatosis) and an increase in lipid peroxidation in liver were observed. Liver and urine samples were analyzed by nuclear magnetic resonance spectroscopy and electrospray infusion/Fourier transform ion cyclotron resonance-mass spectrometry. In livers of alcohol-treated mice the following changes were noted. Hypoxia and glycolysis were activated as evidenced by elevated levels of alanine and lactate. Tyrosine, which is required for L-DOPA and dopamine as well as thyroid hormones, was elevated possibly reflecting alterations of basal metabolism by alcohol. A 4-fold increase inmore » the prostacyclin inhibitor 7,10,13,16-docosatetraenoic acid, a molecule important for regulation of platelet formation and blood clotting, may explain why chronic drinking causes serious bleeding problems. Metabolomic analysis of the urine revealed that alcohol treatment leads to decreased excretion of taurine, a metabolite of glutathione, and an increase in lactate, n-acetylglutamine and n-acetylglycine. Changes in the latter two metabolites suggest an inhibition of the kidney enzyme aminoacylase I and may be useful as markers for alcohol consumption.« less

Authors:
 [1];  [2]; ; ; ;  [1];  [2];  [3];  [1]
  1. Department of Environmental Sciences and Engineering, 0031 Michael Hooker Research Center, CB 7431, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7431 (United States)
  2. Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States)
  3. First Department of Surgery, University of Yamanashi, Yamanashi (Japan)
Publication Date:
OSTI Identifier:
21144140
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 232; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2008.06.022; PII: S0041-008X(08)00270-6; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALANINES; ALCOHOLS; CORN OIL; DOPA; ENZYMES; FOURIER TRANSFORMATION; GLUTATHIONE; INFLAMMATION; INJURIES; LIVER; MASS SPECTROSCOPY; MICE; NUCLEAR MAGNETIC RESONANCE; TAURINE; THYROID HORMONES; TYROSINE; URINE

Citation Formats

Bradford, Blair U, O'Connell, Thomas M, Han, Jun, Kosyk, Oksana, Shymonyak, Svitlana, Ross, Pamela K, Winnike, Jason, Kono, Hiroshi, and Rusyn, Ivan. Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease. United States: N. p., 2008. Web. doi:10.1016/j.taap.2008.06.022.
Bradford, Blair U, O'Connell, Thomas M, Han, Jun, Kosyk, Oksana, Shymonyak, Svitlana, Ross, Pamela K, Winnike, Jason, Kono, Hiroshi, & Rusyn, Ivan. Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease. United States. https://doi.org/10.1016/j.taap.2008.06.022
Bradford, Blair U, O'Connell, Thomas M, Han, Jun, Kosyk, Oksana, Shymonyak, Svitlana, Ross, Pamela K, Winnike, Jason, Kono, Hiroshi, and Rusyn, Ivan. 2008. "Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease". United States. https://doi.org/10.1016/j.taap.2008.06.022.
@article{osti_21144140,
title = {Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease},
author = {Bradford, Blair U and O'Connell, Thomas M and Han, Jun and Kosyk, Oksana and Shymonyak, Svitlana and Ross, Pamela K and Winnike, Jason and Kono, Hiroshi and Rusyn, Ivan},
abstractNote = {Metabolomic evaluation of urine and liver was conducted to assess the biochemical changes that occur as a result of alcohol-induced liver injury. Male C57BL/6J mice were fed an isocaloric control- or alcohol-containing liquid diet with 35% of calories from corn oil, 18% protein and 47% carbohydrate/alcohol for up to 36 days ad libitum. Alcohol treatment was initiated at 7 g/kg/day and gradually reached a final dose of 21 g/kg/day. Urine samples were collected at 22, 30 and 36 days and, in additional treatment groups, liver and serum samples were harvested at 28 days. Steatohepatitis was induced in the alcohol-fed group since a 5-fold increase in serum alanine aminotransferase activity, a 6-fold increase in liver injury score (necrosis, inflammation and steatosis) and an increase in lipid peroxidation in liver were observed. Liver and urine samples were analyzed by nuclear magnetic resonance spectroscopy and electrospray infusion/Fourier transform ion cyclotron resonance-mass spectrometry. In livers of alcohol-treated mice the following changes were noted. Hypoxia and glycolysis were activated as evidenced by elevated levels of alanine and lactate. Tyrosine, which is required for L-DOPA and dopamine as well as thyroid hormones, was elevated possibly reflecting alterations of basal metabolism by alcohol. A 4-fold increase in the prostacyclin inhibitor 7,10,13,16-docosatetraenoic acid, a molecule important for regulation of platelet formation and blood clotting, may explain why chronic drinking causes serious bleeding problems. Metabolomic analysis of the urine revealed that alcohol treatment leads to decreased excretion of taurine, a metabolite of glutathione, and an increase in lactate, n-acetylglutamine and n-acetylglycine. Changes in the latter two metabolites suggest an inhibition of the kidney enzyme aminoacylase I and may be useful as markers for alcohol consumption.},
doi = {10.1016/j.taap.2008.06.022},
url = {https://www.osti.gov/biblio/21144140}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 232,
place = {United States},
year = {Wed Oct 15 00:00:00 EDT 2008},
month = {Wed Oct 15 00:00:00 EDT 2008}
}