Liquid chromatography mass spectrometry-based profiling of phosphatidylcholine and phosphatidylethanolamine in the plasma and liver of acetaminophen-induced liver injured mice

Lipids Health Dis. 2017 Aug 14;16(1):153. doi: 10.1186/s12944-017-0540-4.

Abstract

Background: Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure in many countries. The aim of the study was to describe the profiling of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and liver of Acetaminophen -induced liver injured mice.

Methods: A time course study was carried out using C57BL/6 mice after intraperitoneal administration of 300 mg/kg Acetaminophen 1 h, 3 h, 6 h, 12 h and 24 h. A high-throughput liquid chromatography mass spectrometry (LC-MS) lipidomic method was utilized to detect phosphatidylcholine and phosphatidylethanolamine species in the plasma and liver. The expressions of phosphatidylcholine and phosphatidylethanolamine metabolism related genes in liver were detected by quantitative Reverse transcription polymerase chain reaction (qRT-PCR) and Western-blot.

Results: Following Acetaminophen treatment, the content of many PC and PE species in plasma increased from 1 h time point, peaked at 3 h or 6 h, and tended to return to baseline at 24 h time point. The relative contents of almost all PC species in liver decreased from 1 h, appeared to be lowest at 6 h, and then return to normality at 24 h, which might be partly explained by the suppression of phospholipases mRNA expressions and the induction of choline kinase (Chka) expression. Inconsistent with PC profile, the relative contents of many PE species in liver increased upon Acetaminophen treatment, which might be caused by the down-regulation of phosphatidylethanolamine N-methyltransferase (Pemt).

Conclusions: Acetaminophen overdose induced dramatic change of many PC and PE species in plasma and liver, which might be caused by damaging hepatocytes and interfering the phospholipid metabolism in Acetaminophen -injured liver.

Keywords: Acetaminophen; Lipidomics; Liver injury; Phosphatidylcholine; Phosphatidylethanolamine.

MeSH terms

  • Acetaminophen / adverse effects*
  • Animals
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Chemical and Drug Induced Liver Injury / pathology
  • Choline Kinase / genetics
  • Choline Kinase / metabolism
  • Chromatography, Liquid
  • Gene Expression Regulation
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Injections, Intraperitoneal
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylcholines / metabolism*
  • Phosphatidylethanolamine N-Methyltransferase / genetics
  • Phosphatidylethanolamine N-Methyltransferase / metabolism
  • Phosphatidylethanolamines / metabolism*
  • Phospholipases / genetics
  • Phospholipases / metabolism

Substances

  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • Acetaminophen
  • phosphatidylethanolamine
  • Phosphatidylethanolamine N-Methyltransferase
  • Choline Kinase
  • Phospholipases