Targeted liquid chromatography-mass spectrometry analysis of serum acylcarnitines in acetaminophen toxicity in children. Biomark Med 2014;8(2):147-59
Date
02/14/2014Pubmed ID
24521011Pubmed Central ID
PMC4125006DOI
10.2217/bmm.13.150Scopus ID
2-s2.0-84894349100 (requires institutional sign-in at Scopus site) 57 CitationsAbstract
AIM: Long-chain acylcarnitines have been postulated to be sensitive biomarkers of acetaminophen (APAP)-induced hepatotoxicity in mouse models. In the following study, the relationship of acylcarnitines with other known indicators of APAP toxicity was examined in children receiving low-dose (therapeutic) and high-dose ('overdose' or toxic ingestion) exposure to APAP.
MATERIALS & METHODS: The study included three subject groups: group A (therapeutic dose, n = 187); group B (healthy controls, n = 23); and group C (overdose, n = 62). Demographic, clinical and laboratory data were collected for each subject. Serum samples were used for measurement of APAP protein adducts, a biomarker of the oxidative metabolism of APAP and for targeted metabolomics analysis of serum acylcarnitines using ultra performance liquid chromatography-triple-quadrupole mass spectrometry.
RESULTS: Significant increases in oleoyl- and palmitoyl-carnitines were observed with APAP exposure (low dose and overdose) compared with controls. Significant increases in serum ALT, APAP protein adducts and acylcarnitines were observed in overdose children that received delayed treatment (time to treatment from overdose >24 h) with the antidote N-acetylcysteine. Time to peak APAP protein adducts in serum was shorter than that of the acylcarnitines and serum ALT.
CONCLUSION: Perturbations in long-chain acylcarnitines in children with APAP toxicity suggest that mitochrondrial injury and associated impairment in the β-oxidation of fatty acids are clinically relevant as biomarkers of APAP toxicity.
Author List
Bhattacharyya S, Yan K, Pence L, Simpson PM, Gill P, Letzig LG, Beger RD, Sullivan JE, Kearns GL, Reed MD, Marshall JD, Van Den Anker JN, James LPAuthors
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of WisconsinKe Yan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AcetaminophenAcetylcysteine
Adolescent
Age Factors
Alanine Transaminase
Biomarkers
Carnitine
Chemical and Drug Induced Liver Injury
Child
Child, Preschool
Chromatography, High Pressure Liquid
Discriminant Analysis
Female
Humans
Least-Squares Analysis
Male
Mass Spectrometry
Metabolomics
Sex Factors