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Title: Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats

Abstract

Metabonomics has already been used to discriminate different pathological states in biological fields. The metabolic profiles of chronic experimental fibrosis and cirrhosis induction in rats were investigated using {sup 1}H NMR spectroscopy of liver extracts and serum combined with pattern recognition techniques. Rats were continuously administered with thioacetamide (TAA) in the drinking water (300 mg TAA/L), and sacrificed on 1st, 2nd, and 3rd month of treatment. {sup 1}H NMR spectra of aqueous and lipid liver extracts, together with serum were subjected to Principal Component Analysis (PCA). Liver portions were also subjected to histopathological examination and biochemical determination of malondialdehyde (MDA). Liver fibrosis and cirrhosis were progressively induced in TAA-treated rats, verified by the histopathological examination and the alterations of MDA levels. TAA administration revealed a number of changes in the {sup 1}H NMR spectra compared to control samples. The performance of PCA in liver extracts and serum, discriminated the control samples from the fibrotic and cirrhotic ones. Metabolic alterations revealed in NMR spectra during experimental liver fibrosis and cirrhosis induction, characterize the stage of fibrosis and could be illustrated by subsequent PCA of the spectra. Additionally, the PCA plots of the serum samples presented marked clustering during fibrosis progression andmore » could be extended in clinical diagnosis for the management of cirrhotic patients.« less

Authors:
 [1];  [2];  [3];  [4]
  1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimioupolis Zografou, 15771 Athens (Greece)
  2. (Greece)
  3. Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75, Mikras Asias str., 11527 Athens (Greece)
  4. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimioupolis Zografou, 15771 Athens (Greece). E-mail: mikros@pharm.uoa.gr
Publication Date:
OSTI Identifier:
20976833
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 218; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2006.10.007; PII: S0041-008X(06)00364-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DIAGNOSIS; DRINKING WATER; FIBROSIS; HYDROGEN 1; INJURIES; LIPIDS; LIVER; NMR SPECTRA; NUCLEAR MAGNETIC RESONANCE; PATIENTS; PATTERN RECOGNITION; PERFORMANCE; RATS; SPECTROSCOPY

Citation Formats

Constantinou, Maria A., Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75, Mikras Asias str., 11527 Athens, Theocharis, Stamatios E., and Mikros, Emmanuel. Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats. United States: N. p., 2007. Web. doi:10.1016/j.taap.2006.10.007.
Constantinou, Maria A., Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75, Mikras Asias str., 11527 Athens, Theocharis, Stamatios E., & Mikros, Emmanuel. Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats. United States. doi:10.1016/j.taap.2006.10.007.
Constantinou, Maria A., Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75, Mikras Asias str., 11527 Athens, Theocharis, Stamatios E., and Mikros, Emmanuel. Mon . "Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats". United States. doi:10.1016/j.taap.2006.10.007.
@article{osti_20976833,
title = {Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats},
author = {Constantinou, Maria A. and Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75, Mikras Asias str., 11527 Athens and Theocharis, Stamatios E. and Mikros, Emmanuel},
abstractNote = {Metabonomics has already been used to discriminate different pathological states in biological fields. The metabolic profiles of chronic experimental fibrosis and cirrhosis induction in rats were investigated using {sup 1}H NMR spectroscopy of liver extracts and serum combined with pattern recognition techniques. Rats were continuously administered with thioacetamide (TAA) in the drinking water (300 mg TAA/L), and sacrificed on 1st, 2nd, and 3rd month of treatment. {sup 1}H NMR spectra of aqueous and lipid liver extracts, together with serum were subjected to Principal Component Analysis (PCA). Liver portions were also subjected to histopathological examination and biochemical determination of malondialdehyde (MDA). Liver fibrosis and cirrhosis were progressively induced in TAA-treated rats, verified by the histopathological examination and the alterations of MDA levels. TAA administration revealed a number of changes in the {sup 1}H NMR spectra compared to control samples. The performance of PCA in liver extracts and serum, discriminated the control samples from the fibrotic and cirrhotic ones. Metabolic alterations revealed in NMR spectra during experimental liver fibrosis and cirrhosis induction, characterize the stage of fibrosis and could be illustrated by subsequent PCA of the spectra. Additionally, the PCA plots of the serum samples presented marked clustering during fibrosis progression and could be extended in clinical diagnosis for the management of cirrhotic patients.},
doi = {10.1016/j.taap.2006.10.007},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 218,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}