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    
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, 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 are different from those induced at 10, The biochemical profiles of 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 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.
Chang Shi; Chun-Qi Wu; An-Min Cao; He-Zhang Sheng; Xian-Zhong Yan; Ming-Yang Liao
Related Documents :
2065855 - Effects of glycogen stores and non-esterified fatty acid availability on insulin-stimul...
3789655 - Effects of feeding high-fat diets to rats: metabolism of erucic acid (c 22:1 n-9) in th...
8199305 - Metabolism of the chlorofluorocarbon substitute 1,1-dichloro-2,2,2-trifluoroethane by r...
10607365 - Changes in free amino acid synthesis in the perfused liver of an air-breathing walking ...
6512535 - Biotransformation of olivetol by syncephalastrum racemosum.
15075465 - Gastric analysis with fractional test meals (ethanol, caffeine, and peptone meal), augm...
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    
Beijing Institute of Pharmacology and Toxicology, 27# Taiping Road, Beijing 100850, PR China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
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*
Mitochondria, Liver / drug effects,  metabolism
Pattern Recognition, Automated
Principal Component Analysis
Pyridines / toxicity*
Pyrimidines / toxicity*
Rats, Wistar
Toxicity Tests / methods*
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

Previous Document:  Antileishmanial polyphenols from Garcinia vieillardii.
Next Document:  Medical potential of plants used by the Q'eqchi Maya of Livingston, Guatemala for the treatment of w...