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- Title
Urinary Metabolic Fingerprinting for α-naphthylisothiocyanate-induced Intrahepatic Cholestasis in Rats Using Fourier Transform-ion Cyclotron Resonance Mass Spectrometry.
- Authors
HASEGAWA, MINA; IDE, MIKA; FUJITA, TAKUYA; TAKENAKA, SHIGEO
- 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.
- Subjects
URINALYSIS; CHOLESTASIS; LABORATORY rats; ION cyclotron resonance spectrometry; ALANINE aminotransferase; ASPARTATE aminotransferase; ALKALINE phosphatase; HEPATOTOXICOLOGY
- Publication
Toxicologic Pathology, 2008, Vol 36, Issue 6, p818
- ISSN
0192-6233
- Publication type
Article
- DOI
10.1177/0192623308323622