Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease

Eric J. Ditzel, Hui Li, Caroline E. Foy, Alec B. Perrera, Patricia Parker, Benjamin J. Renquist, Nathan J. Cherrington, Todd D. Camenisch

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Non-alcoholic fatty liver disease can result in changes to drug metabolism and disposition potentiating adverse drug reactions. Furthermore, arsenite exposure during development compounds the severity of diet-induced fatty liver disease. This study examines the effects of arsenite potentiated diet-induced fatty liver disease on hepatic transport in male mice. Changes were detected for Mrp2/3/4 hepatic transporter gene expression as well as for Oatp1a4/2b1/1b2. Plasma concentrations of Mrp and Oatp substrates were increased in arsenic exposure groups compared with diet-only controls. In addition, murine embryonic hepatocytes and adult primary hepatocytes show significantly altered transporter expression after exposure to arsenite alone: a previously unreported phenomenon. These data indicate that developmental exposure to arsenite leads to changes in hepatic transport which could increase the risk for ADRs during fatty liver disease.

Original languageEnglish (US)
Pages (from-to)321-330
Number of pages10
JournalJournal of Biochemical and Molecular Toxicology
Volume30
Issue number7
DOIs
StatePublished - Jul 1 2016

Keywords

  • Arsenic
  • Development
  • Fatty Liver Disease
  • Transport

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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