Nevirapine Biotransformation Insights: An Integrated In Vitro Approach Unveils the Biocompetence and
3D culture
glutathione
hepatocytes
metabolism
nevirapine
stem cells
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
03 Jun 2020
03 Jun 2020
Historique:
received:
22
04
2020
revised:
20
05
2020
accepted:
29
05
2020
entrez:
7
6
2020
pubmed:
7
6
2020
medline:
1
4
2021
Statut:
epublish
Résumé
The need for competent in vitro liver models for toxicological assessment persists. The differentiation of stem cells into hepatocyte-like cells (HLC) has been adopted due to its human origin and availability. Our aim was to study the usefulness of an in vitro 3D model of mesenchymal stem cell-derived HLCs. 3D spheroids (3D-HLC) or monolayer (2D-HLC) cultures of HLCs were treated with the hepatotoxic drug nevirapine (NVP) for 3 and 10 days followed by analyses of Phase I and II metabolites, biotransformation enzymes and drug transporters involved in NVP disposition. To ascertain the toxic effects of NVP and its major metabolites, the changes in the glutathione net flux were also investigated. Phase I enzymes were induced in both systems yielding all known correspondent NVP metabolites. However, 3D-HLCs showed higher biocompetence in producing Phase II NVP metabolites and upregulating Phase II enzymes and
Identifiants
pubmed: 32503263
pii: ijms21113998
doi: 10.3390/ijms21113998
pmc: PMC7312429
pii:
doi:
Substances chimiques
Solvents
0
Xenobiotics
0
Nevirapine
99DK7FVK1H
Glutathione
GAN16C9B8O
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fundação para a Ciência e a Tecnologia
ID : PTDC/MED-TOX/29183/2017
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