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An integrated metabonomic approach to describe temporal metabolic disregulation induced in the rat by the model hepatotoxin allyl formate

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. ORCID: 0000-0003-1550-4482, Hanton, Gilles, Provost, Jean-Pierre, Le Net, Jean-Loic, Charuel, Claude, Lindon, John C. and 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). pp. 2675-2684. ISSN 1535-3893 (Print), 1535-3907 (Online) (doi:10.1021/pr0601584)

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: allyl formate, metabonomics, metabolomics, Magic Angle Spinning, Nuclear Magnetic Resonance, liver, plasma, urine, Partial Least Squares, Orthogonal-Partial Least Squares, pattern recognition
Subjects: Q Science > QL Zoology
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Department of Pharmaceutical, Chemical & Environmental Sciences
Related URLs:
Last Modified: 17 Oct 2016 09:11
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
URI: http://gala.gre.ac.uk/id/eprint/5264

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