Document Detail


NMR-spectroscopy-based metabonomic approach to the analysis of Bay41-4109, a novel anti-HBV compound, induced hepatotoxicity in rats.
MedLine Citation:
PMID:  17826925     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An integrated metabonomics study using high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy has been applied to investigate the biochemical composition of urine, serum, liver tissue aqueous extracts (acetonitrile/water) and liver tissue lipidic extracts (chloroform/methanol) obtained from control and Bay41-4109 treated rats (10, 50, 400mg.kg(-1).d(-1) for 5 days, i.g.). Principal components analysis was used to visualize similarities and differences in biochemical profiles. The results showed the effects induced by Bay41-4109 at 400mg.kg(-1).d(-1) are different from those induced at 10, 50mg.kg(-1).d(-1). The biochemical profiles of 400mg.kg(-1).d(-1) group might reflect the hepatotoxicity of Bay41-4109 more exactly. The elevation in the level of 3-HB, lactate, 2-hydroxy-acetol and d-glucose was found in the urine, and the levels of VLDL/LDL(CH(2))(n), VLDL/LDL-CH(3), 2-oxo-3-methyl-n-valerate, 3-HB, lactate, acetate, taurine, 2-hydroxy-isovalerate in serum were increased significantly in 400mg.kg(-1).d(-1) group. The predominant changes identified in liver tissue aqueous extracts included an increase in the signal intensities of lactate, 3-amino-isovalerate, pyruvate, choline, trimethylamine-N-oxide (TMAO) and a reduction in the intensities of taurine, hippurate and d-glucose. In liver tissue chloroform/methanol extracts, there was a remarkably increase in many of the lipid signals including the triglyceride terminal methyl, methylene groups, and CH(2)CO, N(+)(CH(3))(3), CH(2)OPO(2), CH(2)OCOR. These observations all provide evidence that fatty acid metabolism disorder and mitochondrial inability might contribute to the hepatotoxicity of Bay41-4109. The application of (1)H NMR spectroscopy to an array of biological samples comprising urine, serum and liver tissue extracts yields new insight into the hepatotoxicity of xenobiotics.
Authors:
Chang Shi; Chun-Qi Wu; An-Min Cao; He-Zhang Sheng; Xian-Zhong Yan; Ming-Yang Liao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-02
Journal Detail:
Title:  Toxicology letters     Volume:  173     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-09-20     Completed Date:  2007-11-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  161-7     Citation Subset:  IM    
Affiliation:
Beijing Institute of Pharmacology and Toxicology, 27# Taiping Road, Beijing 100850, PR China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antiviral Agents / toxicity*
Biological Markers / blood,  metabolism*,  urine
Dose-Response Relationship, Drug
Drug-Induced Liver Injury
Fatty Acids / metabolism
Lipid Metabolism / drug effects
Liver / drug effects,  metabolism*
Liver Diseases / blood,  metabolism*,  urine
Magnetic Resonance Spectroscopy*
Male
Mitochondria, Liver / drug effects,  metabolism
Pattern Recognition, Automated
Principal Component Analysis
Pyridines / toxicity*
Pyrimidines / toxicity*
Rats
Rats, Wistar
Toxicity Tests / methods*
Chemical
Reg. No./Substance:
0/Antiviral Agents; 0/BAY 41-4109; 0/Biological Markers; 0/Fatty Acids; 0/Pyridines; 0/Pyrimidines

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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