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题名: Systems toxicology study of doxorubicin on rats using ultra performance liquid chromatography coupled with mass spectrometry based metabolomics
作者: Wang, Jiangshan1, 2;  Reijmers, Theo2;  Chen, Lijuan4;  Van der Heijden, Rob2;  Wang, Mei3;  Peng, Shuangqing4;  Hankemeier, Thomas2;  Xu, Guowang1;  Van der Greef, Jan2, 3
关键词: Metabolomics ;  Doxorubicin ;  UPLC-MS ;  FTMS ;  Systems toxicology
刊名: METABOLOMICS
发表日期: 2009-12-01
DOI: 10.1007/s11306-009-0165-3
卷: 5, 期:4, 页:407-418
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Endocrinology & Metabolism
研究领域[WOS]: Endocrinology & Metabolism
英文摘要: A metabolomics-based systems toxicology approach was used to profile the urinary metabolites for the toxicity related processes and pathogenesis induced by doxorubicin (DOX) to rats. Endogenous metabolite profiles were obtained with ultra performance liquid chromatography-mass spectrometry (UPLC-MS) for rats receiving different single dosages of DOX (5, 10 or 20 mg/kg) prior and at three time points after dosage. Principal components analysis (PCA) allowed detection of two major systemic metabolic changes with the time due to the induced toxicity. Furthermore, Analysis of variance (ANOVA) Simultaneous Component Analysis (ASCA) was applied to reveal the variation caused by time and dose, and their interaction in a multivariate way. Finally, various metabolites involved in the toxic processes could be identified using their accurate mass and MS(n) experiments, and possible mechanisms of the toxicity of DOX were postulated. In conclusion, metabolomics as a systems toxicology approach was able to provide comprehensive information on the dynamic process of drug induced toxicity. In addition, detection of the systemic toxic effects could be obtained with metabolomics at an earlier stage compared to the clinical chemistry and histopathological assessment.
关键词[WOS]: MITOCHONDRIAL TOXICITY ;  H-1-NMR SPECTROSCOPY ;  HPLC-TOF/MS ;  METABONOMICS ;  NEPHROTOXICITY ;  IDENTIFICATION ;  BIOLOGY ;  URINE ;  CARDIOMYOPATHY ;  HEPATOTOXICITY
语种: 英语
WOS记录号: WOS:000272849800003
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/141507
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
2.Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Analyt Biosci, NL-2300 RA Leiden, Netherlands
3.TNO, Qual Life & BioMed, NL-3700 AJ Zeist, Netherlands
4.Acad Mil Med Sci, Beijing Inst Dis Control & Prevent, Res & Evaluat Ctr Toxicol, Beijing 100071, Peoples R China

Recommended Citation:
Wang, Jiangshan,Reijmers, Theo,Chen, Lijuan,et al. Systems toxicology study of doxorubicin on rats using ultra performance liquid chromatography coupled with mass spectrometry based metabolomics[J]. METABOLOMICS,2009,5(4):407-418.
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