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Metabolites 2017, 7(3), 46;

Metabolomics Analysis of Urine Samples from Children after Acetaminophen Overdose

Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA
Arkansas Children’s Research Institute, Little Rock, AR 72202, USA
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA
Author to whom correspondence should be addressed.
Received: 31 July 2017 / Revised: 1 September 2017 / Accepted: 4 September 2017 / Published: 6 September 2017
(This article belongs to the Special Issue Metabolomics and Its Application in Human Diseases)
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Acetaminophen (APAP), a commonly used over-the-counter analgesic, accounts for approximately fifty percent of the cases of acute liver failure (ALF) in the United States due to overdose, with over half of those unintentional. Current clinical approaches for assessing APAP overdose rely on identifying the precise time of overdose and quantitating acetaminophen alanine aminotransferase (ALT) levels in peripheral blood. Novel specific and sensitive biomarkers may provide additional information regarding patient status post overdose. Previous non-clinical metabolomics studies identified potential urinary biomarkers of APAP-induced hepatotoxicity and metabolites involved pathways of tricarboxylic acid cycle, ketone metabolism, and tryptophan metabolism. In this study, biomarkers identified in the previous non-clinical study were evaluated in urine samples collected from healthy subjects (N = 6, median age 14.08 years) and overdose patients (N = 13, median age 13.91 years) as part of an IRB-approved multicenter study of APAP toxicity in children. The clinical results identified metabolites from pathways previously noted, and pathway analysis indicated analogous pathways were significantly altered in both the rats and humans after APAP overdose. The results suggest a metabolomics approach may enable the discovery of specific, translational biomarkers of drug-induced hepatotoxicity that may aid in the assessment of patients. View Full-Text
Keywords: acetaminophen; biomarker; mass spectrometry; metabolomics; overdose acetaminophen; biomarker; mass spectrometry; metabolomics; overdose

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Schnackenberg, L.K.; Sun, J.; Bhattacharyya, S.; Gill, P.; James, L.P.; Beger, R.D. Metabolomics Analysis of Urine Samples from Children after Acetaminophen Overdose. Metabolites 2017, 7, 46.

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