title: Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease.
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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, USA. eric.ditzel@ecolab.com.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Ditzel
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, 85721, USA.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Foy
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, USA.
authors.forename: Alec B
authors.initials: AB
authors.lastname: Perrera
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Parker
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, 85721, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Renquist
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, USA.|Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, 85721, USA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Cherrington
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, USA.|Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, 85721, USA.|Steele Children's Research Center, Arizona Health Sciences Center, The University of Arizona, Tucson, AZ, 85724, USA.|Sarver Heart Center, The University of Arizona, Tucson, AZ, 85724, USA.|Bio5 Institute, The University of Arizona, Tucson, AZ, 85721, USA.
authors.forename: Todd D
authors.initials: TD
authors.lastname: Camenisch
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001692:Biological Transport / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004622:Embryo, Mammalian; D005260:Female; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D061251:Primary Cell Culture; D015398:Signal Transduction
chemical_list: D042501:Angiogenic Proteins; D018053:Arsenites; D027381:Liver-Specific Organic Anion Transporter 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029362:Organic Anion Transporters, Sodium-Independent; D027701:Organic Cation Transport Proteins; C489540:Abcc4 protein, mouse; C572127:SLCO1A1 protein, mouse; C464433:Oatp2 protein, mouse; C498887:Slco1b2 protein, mouse; C543400:mitogen-regulated protein 3, mouse; C015001:arsenite
keywords: Arsenic; Development; Fatty Liver Disease; Transport