Targeted metabolomic profiling indicates structure-based perturbations in serum phospholipids in children with acetaminophen overdose. Toxicol Rep 2016;3:747-755
Date
09/30/2017Pubmed ID
28959601Pubmed Central ID
PMC5616013DOI
10.1016/j.toxrep.2016.08.004Scopus ID
2-s2.0-84988409871 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
Phospholipids are an important class of lipids that act as building blocks of biological cell membranes and participate in a variety of vital cellular functions including cell signaling. Previous studies have reported alterations in phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) metabolism in acetaminophen (APAP)-treated animals or cell cultures. However, little is known about phospholipid perturbations in humans with APAP toxicity. In the current study, targeted metabolomic analysis of 180 different metabolites including 14 lysoPCs and 73 PCs was performed in serum samples from children and adolescents hospitalized for APAP overdose. Metabolite profiles in the overdose group were compared to those of healthy controls and hospitalized children receiving low dose APAP for treatment of pain or fever (therapeutic group). PCs and lysoPCs with very long chain fatty acids (VLCFAs) were significantly decreased in the overdose group, while those with comparatively shorter chain lengths were increased in the overdose group compared to the therapeutic and control groups. All ether linked PCs were decreased in the overdose group compared to the controls. LysoPC-C26:1 was highly reduced in the overdose group and could discriminate between the overdose and control groups with 100% sensitivity and specificity. The PCs and lysoPCs with VLCFAs showed significant associations with changes in clinical indicators of drug metabolism (APAP protein adducts) and liver injury (alanine aminotransferase, or ALT). Thus, a structure-dependent reduction in PCs and lysoPCs was observed in the APAP-overdose group, which may suggest a structure-activity relationship in inhibition of enzymes involved in phospholipid metabolism in APAP toxicity.
Author List
Bhattacharyya S, Pence L, Yan K, Gill P, Luo C, Letzig LG, Simpson PM, Kearns GL, Beger RD, 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
