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A metabonomic characterization of CCl4-induced acute liver failure using partial least square regression based on the GC/MS metabolic profiles of plasma in mice

Huang, Xin, Shao, Li, Gong, Yifei, Mao, Yong, Liu, Changxiao, Qu, Haibin, Cheng, Yiyu·2008·Journal of Chromatography B
DOI 10.1016/j.jchromb.2008.05.049
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Abstract

This work characterized the metabolism disorders of acute liver failure (ALF) induced by carbon tetrachloride (CCl(4)) in a mouse model with different dosage of intoxication (100, 500 and 1000 mg/kg). Metabolic profiles of mice plasma were detected by gas chromatography/mass spectrometry (GC/MS) after chemical derivatization. Here an effective information-extracting approach was implemented on the basis of partial least square regression analysis (PLS-RA). PLS modeling was achieved with two kinds of Y-vectors for the acquired metabonomics data and eight metabolites with different changing behaviors were selected. ALF of mice induced by CCl(4) was characterized by the elevation of glutamate, citrate, serine and threonine, as well as the decrease of alpha-glycerophosphate, docosahexaenoic acid, palmitic acid and oleic acid in plasma. The difference in the concentrations of serine, threonine, palmitic acid and oleic acid remained insignificant between the control and 100mg/kg groups, while significant distinction appeared when comparing the control and two higher dosed groups. The underlying regulation of CCl(4)-perturbed metabolic pathways was discussed according to the selected metabolites. The present study demonstrated a great potential of PLS-RA in exploiting a comprehensive metabolic effects of CCl(4) intoxication and its efficient capability to reveal the hepatotoxic mechanism of ALF induced by reactive oxygen species (ROS).

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Crossref · 10.1016/j.jchromb.2008.05.049

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  • Adult humans are characterized by individual metabolic phenotypes; metabolic profiles can predict susceptibility to DILI.

    “Adult humans are characterized by individual metabolic phenotypes [37,38,39,40,41]; there are areas of the metabolome unique to each individual that remain stable over time. “Metabolic profiles” can be detected that allow us to predict which individuals may present ways of metabolizing drugs that make them more susceptible to presenting DILI [17].”

    From Metabolomic Analysis of Pediatric Patients with Idiosyncratic Drug-Induced Liver Injury According to the Updated RUCAM (2023) · cites this paper as [38]

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Metadata

Authors
Huang, X., Shao, L., Gong, Y., Mao, Y., Liu, C., Qu, H., & Cheng, Y.
Venue
Journal of Chromatography B
Publisher
Elsevier BV
Published
2008-07
Volume
870
Issue
2
Pages
178-185
ISSN
1570-0232
DOI
10.1016/j.jchromb.2008.05.049
Cited by
43
References
1
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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