Högskolan i Skövde

his.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • apa-cv
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • 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, The Netherlands.ORCID iD: 0000-0003-4697-0590
Division of Pharmacokinetics Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, The Netherlands.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, The Netherlands.
Division of Pharmacokinetics Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, The Netherlands.
Show others and affiliations
2017 (English)In: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738, Vol. 91, no 5, p. 2079-2092Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
Springer, 2017. Vol. 91, no 5, p. 2079-2092
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Bioinformatics; INF502 Biomarkers
Identifiers
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
Note

CC BY 4.0

Erratum in: Archives of Toxicology, volume 91, issue 7, page 2711 (2017). doi:10.1007/s00204-016-1895-4

Received: 7 July 2016 / Accepted: 28 September 2016 / Published online: 7 October 2016

The authors thank Prof. Dr. Robert Porte and all the surgeons of the University Medical Center Groningen for providing the human liver tissue. This study was financially supported by the EU-funded project NanoBio4Trans (Grant No. 304842).

Available from: 2016-10-24 Created: 2016-10-24 Last updated: 2022-12-30Bibliographically approved

Open Access in DiVA

fulltext(2074 kB)182 downloads
File information
File name FULLTEXT01.pdfFile size 2074 kBChecksum SHA-512
6a105d931c4556220e8b6d0f2af6ddaa3f5b7e92bf5f1c51463752450e7b21ef0ff178c7612b0ebe4c8aec082968e29417b556a5f6c70ffa78f6ca3d354d9a75
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopusErratum to: Maintenance of drug metabolism and transport functions in human precision-cut liver slices during prolonged incubation for 5 days

Authority records

Asplund, AnnikaSynnergren, Jane

Search in DiVA

By author/editor
Starokozhko, ViktoriiaAsplund, AnnikaSynnergren, Jane
By organisation
School of BioscienceThe Systems Biology Research Centre
In the same journal
Archives of Toxicology
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Search outside of DiVA

GoogleGoogle Scholar
Total: 182 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 632 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • apa-cv
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf