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Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver

A D B Vliegenthart1, J M Shaffer2, J I Clarke3

  • 1Pharmacology, Toxicology and Therapeutics, University/BHF Centre for Cardiovascular Science, Edinburgh University, UK.

Scientific Reports
|October 23, 2015
PubMed

Insights

New biomarkers for drug-induced liver and kidney injury were identified using microRNA (miRNA) profiling in acetaminophen overdose patients. Specific miRNAs accurately detected liver injury and showed potential for diagnosing kidney dysfunction.

Area of Science:

  • Biochemistry
  • Genomics
  • Toxicology

Background:

  • Drug-induced organ injury, particularly liver and kidney damage, poses a significant clinical challenge.
  • Acetaminophen overdose is a leading cause of acute liver failure.
  • Identifying reliable biomarkers for early detection and monitoring of drug-induced organ injury is crucial.

Purpose of the Study:

  • To identify circulating microRNA (miRNA) biomarkers for drug-induced liver and kidney injury.
  • To profile the miRNome in patients with acetaminophen overdose and organ injury.
  • To develop and validate a miRNA-based diagnostic model for acetaminophen-induced liver toxicity.

Main Methods:

  • Plasma miRNAs were quantified in patients with and without acetaminophen-induced organ injury (APAP-TOX).
  • A 16-miRNA classifier model was developed and tested in a separate cohort.
  • miRNA specificity was assessed in non-acetaminophen liver injury models and murine models; sensitivity was evaluated at hospital presentation.

Main Results:

  • A 16-miRNA classifier model accurately diagnosed acetaminophen-induced liver toxicity in a test cohort.
  • Specific miRNAs (e.g., miR-122-5p, miR-885-5p, miR-151a-3p, miR-382-5p) accurately reported liver injury, independent of kidney injury.
  • A panel of miRNAs was associated with human kidney dysfunction, and certain miRNAs specifically reported acetaminophen toxicity in mice.

Conclusions:

  • Circulating miRNAs can serve as effective biomarkers for acute liver injury induced by acetaminophen.
  • The identified miRNA panel shows potential for diagnosing drug-induced kidney injury.
  • miRNA profiling offers a promising approach for early detection and management of drug-induced organ toxicities.

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