Affiliation:
1. Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka, Japan
2. Exploratory Toxicology and DMPK Research Laboratories, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan
Abstract
Urinary metabolic fingerprinting with Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) was performed to monitor metabolic changes in an α-naphthylisothiocyanate (ANIT)-induced rat model of intrahepatic cholestasis and to investigate the relationships among metabolic changes, histopathology, and blood chemistry. ANIT was administered orally as a single dose of 100 mg/kg. Urine samples were collected predose (–31 to –24 hours) and postdose at 0–7, 7–24, 24–31, 31–48, 48–55, 55–72, and 72–96 hours, and serum samples were collected on days 1, 2, and 4 postdose. Increased levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin were seen on day 2. The negative ion profiles for urine samples collected after 7–24, 24–31, 31–48, and 48–55 hours differed from the predose profile based on principal component analysis. Onset of recovery was observed after 24–31 hours, when the urinary composition reverted toward the predose position. In conclusion, it is possible to monitor the progression of and recovery from drug-induced hepatotoxicity by urinary metabolic fingerprinting with FT-ICR MS and to search for potential biomarkers involved in intrahepatic cholestasis.
Subject
Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine
Cited by
7 articles.
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