Urinary metabolic fingerprinting for thioacetamide-induced rat acute hepatic injury using fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS), with reference to detection of potential biomarkers for hepatotoxicity

In this study, we performed urinary metabolic fingerprinting using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) in the thioacetamide (TAA)-induced rat model of acute hepatic injury to search for useful biomarkers involved in the acute hepatic toxicity. TAA was intraperiton...

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Bibliographic Details
Published inToxicologic pathology Vol. 35; no. 4; p. 570
Main Authors Hasegawa, Mina, Ide, Mika, Takenaka, Shigeo, Yamate, Jyoji, Tsuyama, Shingo
Format Journal Article
LanguageEnglish
Published United States 01.06.2007
Subjects
Alanine Transaminase - blood
Animals
Aspartate Aminotransferases - blood
Biomarkers
Chemical and Drug Induced Liver Injury - pathology
Chemical and Drug Induced Liver Injury - urine
Cyclotrons
Fourier Analysis
Liver - pathology
Macrophages - pathology
Male
Mass Spectrometry
Principal Component Analysis
Rats
Rats, Inbred F344
Thioacetamide - toxicity
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Summary:In this study, we performed urinary metabolic fingerprinting using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) in the thioacetamide (TAA)-induced rat model of acute hepatic injury to search for useful biomarkers involved in the acute hepatic toxicity. TAA was intraperitonealy administered a single dose of 300 mg/kg, and urine sample and livers were collected on predose, and days 1, 3, 5, and 7 postdose (Days 1, 3, 5, and 7). Histopathologically, infiltration of macrophages occurred in the TAA-induced centrilobular injured area on Days 1 and 3, and the injured liver recovered on Days 5 and 7. On the scores plot of principal component analysis (PCA), the ion profiles of Days 1 and 3 were different from those of the predose, Days 5 and 7. The loading plot revealed that the metabolites causing PCA results were m/z 266.05390, 401.20737, and 429.23882. The ion at m/z 266.05390 was identified as a potassium ion adduct of deoxycytidine (dCyt). Because the appearance of urinary dCyt was corresponding to macrophage infiltration in the rat-injured liver, it was considered that the urinary dCyt might be released from infiltrated macrophages. dCty might be a biomarker for the acute hepatotoxicity in rats.
ISSN:0192-6233