2019

CYP1A2 Enzyme Localization in Normal and Diseased Pediatric Livers

Published:  13 March 2019

B. W. Ogilvie1, M. Czerwinski1, A. Kats2, M. T. Pritchard3,4, and S. E. Tague5.
1Sekisui XenoTech LLC, Kansas City, KS; 2Department of Pathology and Laboratory Medicine, Children’s Mercy Hospital, Kansas City, MO; 3Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS; 4The Liver Center, University of Kansas Medical Center, Kansas City, KS; and 5Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS

CYP1A2 is a Phase 1 drug metabolizing enzyme whose expression begins between birth and 4 weeks of age, and gradually increases to about half of the adult levels by 6 years of age. The enzyme is expressed predominantly in liver where it constitutes 4 - 16% of the total hepatic CYP pool, and is a major determinant of the biotransformation of ~9% of clinically used drugs. Interestingly, CYP1A2 activity is decreased in adults with non-alcoholic fatty liver disease (NAFLD). Considering the increase in the number of medications given to children, as well as the rise in childhood obesity and NAFLD, this study utilized a pediatric liver tissue microarray (TMA) to determine if CYP1A2 abundance and localization was influenced by donor age and disease...

As this was selected to be a 20-min. Xenobiotic Disposition in Disease and Toxicities Topic platform presentation at the Society of Toxicology (SOT) Meeting & ToxExpo, no poster was presented. However, you may request information from the presentation or a webinar on the topic.

Patterns of Hyaluronan Deposition in Normal and Diseased Pediatric Livers

Published:  13 March 2019

Presented at the March 2019 Annual Society of Toxicology (SOT) Meeting in Baltimore, MD.
Maciej CzerwiƄski1, Alexander Kats2, Jordan Surgnier3, Sarah E. Tague4, and Michele T. Pritchard3,5
1
Sekisui XenoTech, Kansas City, KS., 2Department of Pathology and Laboratory Medicine, Children’s Mercy Hospital, Kansas City, MO., 3Department of Pharmacology, Toxicology and Therapeutics, 4Kansas Intellectual and Developmental Disabilities Research Center, 5The Liver Center, University of Kansas Medical Center, Kansas City, KS

The incidence of obesity and non-alcoholic fatty liver disease (NAFLD) is growing in children. Hyaluronan (HA), an extracellular matrix (ECM) glycosaminoglycan, is increased in liver and blood from adults with advanced liver disease. HA accumulation is also associated with inflammation and fibrosis in extrahepatic tissues. HA levels have not been examined in healthy or diseased livers from pediatric patients. Here, we sought to determine if hepatic HA deposition was associated with donor age and/or disease by using a pediatric liver tissue microarray (TMA)...