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Sci Rep. 2015 Oct 22;5:15501. doi: 10.1038/srep15501.

Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver and kidney injury.

Author information

Pharmacology, Toxicology and Therapeutics, University/BHF Centre for Cardiovascular Science, Edinburgh University, UK.
Qiagen, Fredrick, Maryland, USA.
MRC Centre for Drug Safety Science, Department of Molecular &Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
King's College London, London, UK.
Scottish Liver Transplantation Unit, Royal Infirmary of Edinburgh, Edinburgh, UK.
MRC Centre for Inflammation Research, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh.


Our objective was to identify microRNA (miRNA) biomarkers of drug-induced liver and kidney injury by profiling the circulating miRNome in patients with acetaminophen overdose. Plasma miRNAs were quantified in age- and sex-matched overdose patients with (N = 27) and without (N = 27) organ injury (APAP-TOX and APAP-no TOX, respectively). Classifier miRNAs were tested in a separate cohort (N = 81). miRNA specificity was determined in non-acetaminophen liver injury and murine models. Sensitivity was tested by stratification of patients at hospital presentation (N = 67). From 1809 miRNAs, 75 were 3-fold or more increased and 46 were 3-fold or more decreased with APAP-TOX. A 16 miRNA classifier model accurately diagnosed APAP-TOX in the test cohort. In humans, the miRNAs with the largest increase (miR-122-5p, miR-885-5p, miR-151a-3p) and the highest rank in the classifier model (miR-382-5p) accurately reported non-acetaminophen liver injury and were unaffected by kidney injury. miR-122-5p was more sensitive than ALT for reporting liver injury at hospital presentation, especially combined with miR-483-3p. A miRNA panel was associated with human kidney dysfunction. In mice, miR-122-5p, miR-151a-3p and miR-382-5p specifically reported APAP toxicity - being unaffected by drug-induced kidney injury. Profiling of acetaminophen toxicity identified multiple miRNAs that report acute liver injury and potential biomarkers of drug-induced kidney injury.

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