Nonalcoholic fatty liver disease alters microcystin-LR toxicokinetics and acute toxicity.

Animals Cell Adhesion Molecules / urine Cholesterol / metabolism Choline / metabolism Diet, High-Fat Hepatobiliary Elimination Inflammation / metabolism Kidney / drug effects Liver / drug effects Male Marine Toxins Methionine / deficiency Microcystins / metabolism Non-alcoholic Fatty Liver Disease / chemically induced Organic Anion Transporters / metabolism Protein Phosphatase 2 / metabolism Proteinuria / chemically induced Rats, Sprague-Dawley Toxicokinetics
Acute toxicity Microcystin-LR Nonalcoholic steatohepatitis Toxicokinetics

Journal

Toxicon : official journal of the International Society on Toxinology
ISSN: 1879-3150
Titre abrégé: Toxicon
Pays: England
ID NLM: 1307333

Informations de publication

Date de publication:
15 Apr 2019
Historique:
received: 13 08 2018
revised: 27 02 2019
accepted: 03 03 2019
pubmed: 9 3 2019
medline: 25 6 2019
entrez: 9 3 2019
Statut: ppublish

Résumé

Microcystin-LR (MCLR) is a cyanotoxin produced by blue-green algae that causes liver and kidney toxicities. MCLR toxicity is dependent on cellular uptake through the organic anion transporting polypeptide (OATP) transporters. Nonalcoholic fatty liver disease (NAFLD) progresses through multiple stages, alters expression of hepatic OATPs, and is associated with chronic kidney disease. The purpose of this study was to determine whether NAFLD increases systemic exposure to MCLR and influences acute liver and kidney toxicities. Rats were fed a control diet or two dietary models of NAFLD; methionine and choline deficient (MCD) or high fat/high cholesterol (HFHC). Two studies were performed in these groups: 1) a single dose intravenous toxicokinetic study (20 μg/kg), and 2) a single dose intraperitoneal toxicity study (60 μg/kg). Compared to control rats, plasma MCLR area under the concentration-time curve (AUC) in MCD rats doubled, whereas biliary clearance (Cl

Identifiants

DOI: 10.1016/j.toxicon.2019.03.002 PMID: 30849452 PMC: PMC6447445
pubmed: 30849452
pii: S0041-0101(19)30063-7
doi: 10.1016/j.toxicon.2019.03.002
pmc: PMC6447445
mid: NIHMS1523381
pii:
doi:

Substances chimiques

Cell Adhesion Molecules 0
Havcr1protein, rat 0
Marine Toxins 0
Microcystins 0
Organic Anion Transporters 0
Cholesterol 97C5T2UQ7J
Methionine AE28F7PNPL
Protein Phosphatase 2 EC 3.1.3.16
cyanoginosin LR EQ8332842Y
Choline N91BDP6H0X

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1-8

Subventions

Organisme : NIEHS NIH HHS
ID : K99 ES024455
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES006694
Pays : United States
Organisme : NIEHS NIH HHS
ID : R00 ES024455
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007091
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

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Auteurs

John D Clarke (JD)

Department of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA. Electronic address: j.clarke@wsu.edu.

Anika Dzierlenga (A)

Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, 85721, USA.

Tarana Arman (T)

Department of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA.

Erica Toth (E)

Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, 85721, USA.

Hui Li (H)

Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, 85721, USA.

Katherine D Lynch (KD)

Department of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA.

Dan-Dan Tian (DD)

Department of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA.

Michael Goedken (M)

Rutgers Translational Sciences, Rutgers University, Piscataway, NJ, 08901, USA.

Mary F Paine (MF)

Department of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA.

Nathan Cherrington (N)

Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, 85721, USA.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes de surface › Molécules d'adhérence cellulaire › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Lipides › Lipides membranaires › Stérols › Cholestérol › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Composés chimiques organiques › Composés onium › Composés d'ammonium quaternaire › Choline › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Phénomènes physiologiques › Alimentation et nutrition › Phénomènes physiologiques nutritionnels › Régime alimentaire › Alimentation riche en graisse › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil buccodentaire et de l'appareil digestif › Phénomènes physiologiques de l'appareil digestif › Élimination hépatobiliaire › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Appareil urogénital › Voies urinaires › Rein › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Système digestif › Foie › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Toxines de la flore et de la faune marines › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés soufrés › Méthionine › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Toxines bactériennes › Toxines de cyanobactéries › Microcystines › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Stéatose hépatique › Stéatose hépatique non alcoolique › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Transporteurs d'anions organiques › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphoprotein Phosphatases › Protein Phosphatase 2 › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations urologiques › Protéinurie › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Sprague-Dawley › Nonalcoholic fatty liver disease alters...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Toxicocinétique › Nonalcoholic fatty liver disease alters...