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 (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).
Huang
Xin
X
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Shao
Li
L
Gong
Yifei
Y
Mao
Yong
Y
Liu
Changxiao
C
Qu
Haibin
H
Cheng
Yiyu
Y
D000818:Animals; D002251:Carbon Tetrachloride; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D016018:Least-Squares Analysis; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D025341:Principal Component Analysis; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D002251:Carbon Tetrachloride