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 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.
Hasegawa
Mina
M
Department of Veterinary Science, Graduate School of Life and Environmenal Science, Osaka Prefecture University, Sakai, Osaka, Japan.
Ide
Mika
M
Takenaka
Shigeo
S
Yamate
Jyoji
J
Tsuyama
Shingo
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000652:urine*; D017357:Cyclotrons; D005583:Fourier Analysis; D008099:Liver / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D025341:Principal Component Analysis; D051381:Rats; D011916:Rats, Inbred F344; D013853:Thioacetamide / Q000633:toxicity*
D015415:Biomarkers; D013853:Thioacetamide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase