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Related Experiment Videos

Hyperbaric oxygen reduces acetaminophen toxicity and increases HIF-1alpha expression.

Steven D Salhanick1, Bryan Belikoff, Daniel Orlow

  • 1Program in Toxicology, Division of Emergency Medicine, Children's Hospital, Boston, MA, USA.

Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine
|April 26, 2006
PubMed
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Hyperbaric oxygen therapy (HBO2) effectively reduced liver injury from acetaminophen (APAP) overdose. While HBO2 increased hypoxia-inducible factor 1-alpha (HIF-1alpha) protein and DNA binding, its transcriptional activity was not enhanced.

Area of Science:

  • Hepatology and Toxicology
  • Biomedical Research
  • Oxygen Therapy

Background:

  • Acetaminophen (APAP) overdose is a leading cause of acute liver failure.
  • Hypoxia-inducible factor 1-alpha (HIF-1alpha) plays a role in cellular response to hypoxia and injury.
  • Hyperbaric oxygen (HBO2) therapy is used for various medical conditions, but its role in APAP-induced hepatotoxicity is not fully understood.

Purpose of the Study:

  • To investigate the therapeutic effect of HBO2 on APAP-induced hepatotoxicity in a mouse model.
  • To evaluate the impact of APAP and HBO2 on HIF-1alpha expression and function.
  • To elucidate the mechanisms underlying APAP hepatotoxicity and the potential role of HBO2.

Main Methods:

  • In vivo study using C57BL/6 mice divided into four groups: APAP only, APAP + HBO2, HBO2 only, and sham.

Related Experiment Videos

  • Measurement of plasma alanine aminotransferase (ALT) activity and hepatic HIF-1alpha expression via Western blot.
  • In vitro study using cultured HEP G2 hepatocytes exposed to HBO2, hypoxia, or normoxia to assess HIF-1alpha DNA-binding and transcriptional activity.

    • Main Results:

    • HBO2 treatment significantly reduced plasma ALT levels in APAP-treated mice compared to APAP-only treatment (p=0.01 at 6 hours).
    • APAP, HBO2, and combined treatments increased hepatic HIF-1alpha expression relative to shams (p<0.01).
    • HBO2 exposure increased HIF-1alpha DNA binding 5.7-fold (p<0.01) but did not enhance its transcriptional activity in vitro.

    Conclusions:

    • Hyperbaric oxygen therapy demonstrates a protective effect against early-stage acetaminophen-induced liver injury.
    • Acetaminophen poisoning elevates both HIF-1alpha protein levels and functional activity.
    • HBO2 increases HIF-1alpha protein levels and DNA binding capacity, independent of a corresponding rise in transcriptional activity.