Lipidomic Profiling Reveals Disruption of Lipid Metabolism in Valproic Acid-Induced Hepatotoxicity

Frontiers in Pharmacology
Shansen XuLimei Zhao

Abstract

Valproic acid (VPA) is one of the most widely prescribed antiepileptic drugs, as VPA-induced hepatotoxicity is one of the most severe adverse reaction that can lead to death. The objective of this study was to gain an understanding of dysregulated lipid metabolism in mechanism of hepatotoxicity. Nontargeted lipidomics analysis with liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF/MS) was performed to explore differential lipids from the patient serum and L02 cells. Lipidomics data interpretation was augmented by gene expression analyses for the key enzymes in lipid metabolism pathways. From patient serum lipidomics, pronouncedly changed lipid species between abnormal liver function (ALF) patients and normal liver function (NLF) patients were identified. Among these lipid species, LPCs, Cers, and SMs were markedly reduced in the ALF group and showed negative relationships with liver injury severity [alanine aminotransferase (ALT) levels], while significantly increased triacylglycerols (TAG) with higher summed carbon numbers demonstrated a positive relationship with ALT levels. Regarding lipidomics in hepatic L02 cells, TAG was markedly elevated after VPA exposure, especially in TAGs with more than 53 s...Continue Reading

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Citations

Jul 29, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Caixia YanYan Liang
Feb 27, 2020·Molecular Pharmacology·Zhibo GaiGerd A Kullak-Ublick
Jan 18, 2021·Drug Metabolism and Pharmacokinetics·Kosuke Saito
Mar 19, 2021·Frontiers in Cell and Developmental Biology·Ana S SerrasJoana P Miranda

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Methods Mentioned

BETA
Assay
protein assay
PCR
PCA

Software Mentioned

LipidView
ImageJ
PLS
PeakView
GraphPad Prism
SPSS
DA
MarkerView
MultiQuant
Prism

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