Document Detail


Gas chromatography-mass spectrometry-based simultaneous quantitative analytical method for urinary oxysterols and bile acids in rats.
MedLine Citation:
PMID:  20875389     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
A simultaneous quantitative assay method for urinary oxysterols and bile acids using GC-MS was developed to investigate the mechanism of liver toxicity induced by drugs or chemicals. Sample preparations were optimized by exploring various extraction solvents, derivatization reagents, and hydrolysis methods to achieve reliable and maximum sensitivity for these two different compound classes. As a result, satisfactory accuracy, precision, and sensitivity were obtained in the validation. The method was then applied to quantify urinary oxysterols and bile acids produced from liver toxicity induced by atorvastatin (250 mg/kg/day). From the results, increases in bile acid levels and decreases in the concentration ratio between cholic acid and chenodeoxycholic acid, which are the distinguishing phenomena observed in serum or bile for liver toxicity, were also observed in urine. Additionally, the mechanism of liver toxicity was investigated with the urinary concentration ratio of product to precursor in the metabolic pathway from cholesterol to bile acids. The results indicated that enzyme activities related to the production and degradation of bile acids, not oxysterols, were significantly changed from liver toxicity. Thus, it was concluded that urinary levels of oxysterols and bile acids could be useful tools for checking liver toxicity and investigating its mechanism.
Authors:
Bhowmik Salil Kumar; Bong Chul Chung; Young-Joo Lee; Hong Jae Yi; Byung-Hoon Lee; Byung Hwa Jung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-25
Journal Detail:
Title:  Analytical biochemistry     Volume:  408     ISSN:  1096-0309     ISO Abbreviation:  Anal. Biochem.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370535     Medline TA:  Anal Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  242-52     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Integrated Omics Center, Korea Institute of Science and Technology, Seoul, Republic of Korea.
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