Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity. PLoS One 2015;10(7):e0131010
Date
07/25/2015Pubmed ID
26208104Pubmed Central ID
PMC4514842DOI
10.1371/journal.pone.0131010Scopus ID
2-s2.0-84941662768 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
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.
Author List
James L, Yan K, Pence L, Simpson P, Bhattacharyya S, Gill P, Letzig L, Kearns G, Beger RAuthors
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
AcetaminophenAdolescent
Alanine Transaminase
Bile Acids and Salts
Biomarkers
Chemical and Drug Induced Liver Injury
Child
Child, Preschool
Diagnosis, Differential
Drug Overdose
Female
Glycochenodeoxycholic Acid
Glycodeoxycholic Acid
Homeostasis
Humans
Male
Metabolomics
Protein Binding
Sensitivity and Specificity
Taurodeoxycholic Acid
