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Metabolomics Analysis of Urine Samples from Children after Acetaminophen Overdose

Laura K Schnackenberg1, Jinchun Sun2, Sudeepa Bhattacharyya3,4

  • 1Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA. laura.schnackenberg@fda.hhs.gov.

Metabolites
|September 8, 2017
PubMed

Insights

Acetaminophen overdose can cause acute liver failure. This study identified novel urinary biomarkers in children, suggesting metabolomics can help assess drug-induced liver injury.

Area of Science:

  • Biochemistry
  • Toxicology
  • Pediatrics

Background:

  • Acetaminophen (APAP) overdose is a leading cause of acute liver failure (ALF) in the US, often unintentional.
  • Current assessment relies on overdose timing and ALT levels, lacking specific biomarkers for patient status.
  • Previous studies identified potential urinary biomarkers for APAP-induced hepatotoxicity in animal models.

Purpose of the Study:

  • To evaluate previously identified urinary biomarkers in a pediatric population with APAP overdose.
  • To determine if metabolomics can identify translational biomarkers for drug-induced hepatotoxicity.

Main Methods:

  • Collected urine samples from healthy children and children with APAP overdose from a multicenter study.
  • Analyzed samples using metabolomics to identify biomarkers.
  • Performed pathway analysis to compare findings between species.

Main Results:

  • Identified metabolites from tricarboxylic acid, ketone, and tryptophan metabolism pathways in human samples.
  • Pathway analysis revealed analogous metabolic alterations in both rats and humans post-APAP overdose.
  • Confirmed translational potential of identified biomarkers.

Conclusions:

  • Metabolomics approach successfully identified and validated urinary biomarkers in pediatric APAP overdose.
  • Findings suggest potential for novel biomarkers to aid in assessing drug-induced hepatotoxicity.
  • This approach may improve patient management and outcomes in APAP toxicity cases.

Keywords:
acetaminophenbiomarkermass spectrometrymetabolomicsoverdose

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