his.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Maintenance of drug metabolism and transport functions in human precision-cut liver slices during prolonged incubation for 5 days
Division of Pharmacokinetics Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Groningen, The Netherlands.ORCID-id: 0000-0003-4697-0590
Division of Pharmacokinetics Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Groningen, The Netherlands.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Division of Pharmacokinetics Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Groningen, The Netherlands.
Visa övriga samt affilieringar
2017 (Engelska)Ingår i: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738, Vol. 91, nr 5, s. 2079-2092Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Human precision-cut liver slices (hPCLS) are a valuable ex vivo model that can be used in acute toxicity studies. However, a rapid decline in metabolic enzyme activity limits their use in studies that require a prolonged xenobiotic exposure. The aim of the study was to extend the viability and function of hPCLS to 5 days of incubation. hPCLS were incubated in two media developed for long-term culture of hepatocytes, RegeneMed(®), and Cellartis(®), and in the standard medium WME. Maintenance of phase I and II metabolism was studied both on gene expression as well as functional level using a mixture of CYP isoform-specific substrates. Albumin synthesis, morphological integrity, and glycogen storage was assessed, and gene expression was studied by transcriptomic analysis using microarrays with a focus on genes involved in drug metabolism, transport and toxicity. The data show that hPCLS retain their viability and functionality during 5 days of incubation in Cellartis(®) medium. Albumin synthesis as well as the activity and gene expression of phase I and II metabolic enzymes did not decline during 120-h incubation in Cellartis(®) medium, with CYP2C9 activity as the only exception. Glycogen storage and morphological integrity were maintained. Moreover, gene expression changes in hPCLS during incubation were limited and mostly related to cytoskeleton remodeling, fibrosis, and moderate oxidative stress. The expression of genes involved in drug transport, which is an important factor in determining the intracellular xenobiotic exposure, was also unchanged. Therefore, we conclude that hPCLS cultured in Cellartis(®) medium are a valuable human ex vivo model for toxicological and pharmacological studies that require prolonged xenobiotic exposure.

Ort, förlag, år, upplaga, sidor
Springer, 2017. Vol. 91, nr 5, s. 2079-2092
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Forskningsämne
Bioinformatik; INF502 Biomarkörer
Identifikatorer
URN: urn:nbn:se:his:diva-13046DOI: 10.1007/s00204-016-1865-xISI: 000399875300004PubMedID: 27717970Scopus ID: 2-s2.0-84991020738OAI: oai:DiVA.org:his-13046DiVA, id: diva2:1039439
Tillgänglig från: 2016-10-24 Skapad: 2016-10-24 Senast uppdaterad: 2019-11-25Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltextPubMedScopus

Personposter BETA

Asplund, AnnikaSynnergren, Jane

Sök vidare i DiVA

Av författaren/redaktören
Starokozhko, ViktoriiaAsplund, AnnikaSynnergren, Jane
Av organisationen
Institutionen för biovetenskapForskningscentrum för Systembiologi
I samma tidskrift
Archives of Toxicology
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 497 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf