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

This work characterized the metabolism disorders of acute liver failure (ALF) induced by carbon tetrachloride (CCl4) 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 CCl4 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 100 mg/kg groups, while significant distinction appeared when comparing the control and two higher dosed groups. The underlying regulation of CCl4-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 CCl4 intoxication and its efficient capability to reveal the hepatotoxic mechanism of ALF induced by reactive oxygen species (ROS). (C) 2008 Elsevier B.V. All rights reserved.