title: Targeted liquid chromatography-mass spectrometry analysis of serum acylcarnitines in acetaminophen toxicity in children.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA and Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
authors: Sudeepa
authors: S
authors: Bhattacharyya
authors: Ke
authors: K
authors: Yan
authors: Lisa
authors: L
authors: Pence
authors: Pippa M
authors: PM
authors: Simpson
authors: Pritmohinder
authors: P
authors: Gill
authors: Lynda G
authors: LG
authors: Letzig
authors: Richard D
authors: RD
authors: Beger
authors: Janice E
authors: JE
authors: Sullivan
authors: Gregory L
authors: GL
authors: Kearns
authors: Michael D
authors: MD
authors: Reed
authors: James D
authors: JD
authors: Marshall
authors: John N
authors: JN
authors: Van Den Anker
authors: Laura P
authors: LP
authors: James
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000111:Acetylcysteine / Q000627:therapeutic use; D000293:Adolescent; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000209:etiology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D016002:Discriminant Analysis; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D012737:Sex Factors
chemical_list: D015415:Biomarkers; C116917:acylcarnitine; D000082:Acetaminophen; D000410:Alanine Transaminase; D002331:Carnitine; D000111:Acetylcysteine