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Urinary Metabolic Fingerprinting for -naphthylisothiocyanate-induced Intrahepatic Cholestasis in Rats Using Fourier Transform-ion Cyclotron Resonance Mass Spectrometry

^* To whom correspondence should be addressed. E-mail: takenaka{at}vet.osakafu-u.ac.jp.

	Abstract

Urinary metabolic fingerprinting with Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) was performed to monitor metabolic changes in an -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.

First published on September 5, 2008, doi:10.1177/0192623308323622

Toxicologic Pathology 2008;36:818.

A more recent version of this article appeared on October 1, 2008


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