An integrated metabonomic approach to describe temporal metabolic disregulation induced in the rat by the model hepatotoxin allyl formate
Yap, Ivan K. S.; Clayton, T. Andrew; Tang, Huiru; Everett, Jeremy R.; Hanton, Gilles; Provost, Jean-Pierre; Le Net, Jean-Loic; Charuel, Claude; Lindon, John C.; Nicholson, Jeremy K.
刊名JOURNAL OF PROTEOME RESEARCH
2006-10-06
卷号5期号:10页码:2675-2684
关键词allyl formate metabonomics metabolomics magic angle spinning nuclear magnetic resonance liver plasma urine partial least squares orthogonal-partial least squares pattern recognition
英文摘要The time-related metabolic events in rat liver, plasma, and urine following hepatotoxic insult with allyl formate (75 mg/kg) were studied using a combination of high-resolution liquid state and magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopic methods together with pattern recognition analysis. The metabonomics results were compared with the results of conventional plasma chemistry and histopathological assessments of liver damage. Various degrees of liver damage were observed in different animals, and this variation was reflected in all of the analyses. Furthermore, each analysis revealed a high degree of functional and structural recovery by the end of the study. The allyl formate-induced changes included hepatocellular necrosis, hepatic lipidosis, decreased liver glycogen and glucose, decreased plasma lipids, increased plasma creatine and tyrosine, increased urinary taurine and creatine, and decreased urinary TCA cycle intermediates. The observed reductions in hepatic glycogen and glucose suggest increased glucose utilization and are consistent with the expected depletion of hepatic ATP following mitochondrial impairment, assuming that there is a consequent increase in energy production from glycolysis. The increase in plasma tyrosine is consistent with impaired protein synthesis, a known consequence of ATP depletion. Partial least squares-based cross-correlation of the variation in the liver and plasma NMR profiles indicated that the allyl formate-induced increase in liver lipids correlated with the decrease in plasma lipids. This suggests disruption in lipid transport from the liver to plasma, which could arise through impaired apolipoprotein synthesis, as with ethionine.
WOS标题词Science & Technology ; Life Sciences & Biomedicine
类目[WOS]Biochemical Research Methods
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]MULTIVARIATE STATISTICAL-ANALYSIS ; MAGNETIC-RESONANCE-SPECTROSCOPY ; SPINNING H-1-NMR SPECTROSCOPY ; NMR-SPECTROSCOPY ; PATTERN-RECOGNITION ; IN-VIVO ; LIQUID-CHROMATOGRAPHY ; GLYCINE CONJUGATION ; MASS-SPECTROMETRY ; LIVER LOBULE
收录类别SCI
语种英语
WOS记录号WOS:000241053100019
公开日期2015-07-28
内容类型期刊论文
源URL[http://ir.wipm.ac.cn/handle/112942/4632]  
专题武汉物理与数学研究所_2011年以前论文发表(包括2011年)
作者单位1.Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Biomol Med, Div Surg Reprod Biol & Anaesthet,SORA, London SW7 2AZ, England
2.Chinese Acad Sci, Wuhan Inst Phys & Math, Wuhan Magnet Resonance Ctr, State Key Lab Magnet Resonance & Mol & Atom Phys, Wuhan 430071, Peoples R China
3.Pfizer Global R7D, Sandwich CT13 9NJ, Kent, England
4.Pfizer Global Res Ctr, Amboise, France
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GB/T 7714
Yap, Ivan K. S.,Clayton, T. Andrew,Tang, Huiru,et al. An integrated metabonomic approach to describe temporal metabolic disregulation induced in the rat by the model hepatotoxin allyl formate[J]. JOURNAL OF PROTEOME RESEARCH,2006,5(10):2675-2684.
APA Yap, Ivan K. S..,Clayton, T. Andrew.,Tang, Huiru.,Everett, Jeremy R..,Hanton, Gilles.,...&Nicholson, Jeremy K..(2006).An integrated metabonomic approach to describe temporal metabolic disregulation induced in the rat by the model hepatotoxin allyl formate.JOURNAL OF PROTEOME RESEARCH,5(10),2675-2684.
MLA Yap, Ivan K. S.,et al."An integrated metabonomic approach to describe temporal metabolic disregulation induced in the rat by the model hepatotoxin allyl formate".JOURNAL OF PROTEOME RESEARCH 5.10(2006):2675-2684.
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