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PLoS One. 2015 Jul 24;10(7):e0131010. doi: 10.1371/journal.pone.0131010. eCollection 2015.

Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity.

Author information

1
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States of America; Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, United States of America.
2
Medical College of Wisconsin, Milwaukee, WI 53226, United States of America.
3
Division of Systems Biology, National Center for Toxicological Research, Jefferson, AR 72079, United States of America.
4
Division of Pediatric Pharmacology, Medical Toxicology and Therapeutic Innovation, The Children's Mercy Hospital, Kansas City, MO 64108, United States of America.

Abstract

Metabolomics approaches have enabled the study of new mechanisms of liver injury in experimental models of drug toxicity. Disruption of bile acid homeostasis is a known mechanism of drug induced liver injury. The relationship of individual bile acids to indicators of oxidative drug metabolism (acetaminophen protein adducts) and liver injury was examined in children with acetaminophen overdose, hospitalized children with low dose exposure to acetaminophen, and children with no recent exposure to acetaminophen. Nine bile acids were quantified through targeted metabolomic analysis in the serum samples of the three groups. Bile acids were compared to serum levels of acetaminophen protein adducts and alanine aminotransferase. Glycodeoxycholic acid, taurodeoxycholic acid, and glycochenodeoxycholic acid were significantly increased in children with acetaminophen overdose compared to healthy controls. Among patients with acetaminophen overdose, bile acids were higher in subjects with acetaminophen protein adduct values > 1.0 nmol/mL and modest correlations were noted for three bile acids and acetaminophen protein adducts as follows: taurodeoxycholic acid (R=0.604; p<0.001), glycodeoxycholic acid (R=0.581; p<0.001), and glycochenodeoxycholic acid (R=0.571; p<0.001). Variability in bile acids was greater among hospitalized children receiving low doses of acetaminophen than in healthy children with no recent acetaminophen exposure. Compared to bile acids, acetaminophen protein adducts more accurately discriminated among children with acetaminophen overdose, children with low dose exposure to acetaminophen, and healthy control subjects. In children with acetaminophen overdose, elevations of conjugated bile acids were associated with specific indicators of acetaminophen metabolism and non-specific indicators of liver injury.

PMID:
26208104
PMCID:
PMC4514842
DOI:
10.1371/journal.pone.0131010
[Indexed for MEDLINE]
Free PMC Article

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