An NMR-spectroscopy-based Metabonomic approach to the analysis of Bay41-4109,a novel anti-HBV compound, induced hepatotoxicity hi rats
An integrated metabonomics study using highresolution 1H 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 Bay414109 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 elevation of 3HB,lactate,2-hydroxy-acetol,hydroxymaleic acid and dglucose was found in the urine, and the levels of VLDL/LDL(CH2) n, VLDL/LDL-CH3 ,2-oxo-3-methyl-nvalerate,3-HB,lactate, pyruvate,taurine,3-aminoisovalerate,2-hydroxy-isovalerate in serum were increased significantly in 400mg ? -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,taurine,choline,TMAO and a reduction in the intensities of trytophan 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 CH2CO,N+(CH3)3,CH2OPO2,CH2OCOR. The results showed that fatty acid metabolism disorder and mitochondrial inability might contribute to the hepatotoxicity of Bay41-4109. The application of 1H NMR spectroscopy to an array of biological samples comprising u-rine,serum and liver tissue extracts yields new insight into the hepatotoxicity of xenobiotics.
Chang SHI Chunqi WU Aiunin CAO HeZhang SHENG Mingyang LIAO
Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China
国际会议
天津
英文
107-110
2011-09-20（万方平台首次上网日期，不代表论文的发表时间）