Nevirapine biotransformation insights
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/99536 |
Resumo: | Funding: This work was supported by FCT (Portugal) through the research grant PTDC/MED-TOX/29183/2017. Acknowledgments: The authors thank ECBio S.A. for providing the hnMSCs and F.A. Beland (NCTR, Jefferson, AR, USA) for the kind donation of nevirapine. FCT (UID/DTP/04138/2019, UID/QUI/00100/2019, RECI/QEQ-MED/0330/2012, SFRH/BD/144130/2019 to J.S.R., SFRH/BD/110945/2015 to P.F.P. and CEECIND/02001/2017 to A.M.M.A) are also acknowledged. |
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Nevirapine biotransformation insightsAn integrated in vitro approach unveils the biocompetence and glutathiolomic profile of a human hepatocyte-like cell 3d model3D cultureGlutathioneHepatocytesMetabolismNevirapineStem cellsCatalysisMolecular BiologySpectroscopyComputer Science ApplicationsPhysical and Theoretical ChemistryOrganic ChemistryInorganic ChemistryFunding: This work was supported by FCT (Portugal) through the research grant PTDC/MED-TOX/29183/2017. Acknowledgments: The authors thank ECBio S.A. for providing the hnMSCs and F.A. Beland (NCTR, Jefferson, AR, USA) for the kind donation of nevirapine. FCT (UID/DTP/04138/2019, UID/QUI/00100/2019, RECI/QEQ-MED/0330/2012, SFRH/BD/144130/2019 to J.S.R., SFRH/BD/110945/2015 to P.F.P. and CEECIND/02001/2017 to A.M.M.A) are also acknowledged.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 MRP7. Accordingly, NVP-exposure led to decreased glutathione availability and alterations in the intracellular dynamics disfavoring free reduced glutathione and glutathionylated protein pools. Overall, these results demonstrate the adequacy of the 3D-HLC model for studying the bioactivation/metabolism of NVP representing a further step to unveil toxicity mechanisms associated with glutathione net flux changes.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNCipriano, MadalenaPinheiro, Pedro F.Sequeira, Catarina O.Rodrigues, Joana S.Oliveira, Nuno G.Antunes, Alexandra M.M.Castro, MatildeMarques, M. MatildePereira, Sofia A.Miranda, Joana P.2020-06-17T22:47:52Z2020-06-012020-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article18application/pdfhttp://hdl.handle.net/10362/99536eng1661-6596PURE: 18621043https://doi.org/10.3390/ijms21113998info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:46:25Zoai:run.unl.pt:10362/99536Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:39:12.197067Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Nevirapine biotransformation insights An integrated in vitro approach unveils the biocompetence and glutathiolomic profile of a human hepatocyte-like cell 3d model |
| title |
Nevirapine biotransformation insights |
| spellingShingle |
Nevirapine biotransformation insights Cipriano, Madalena 3D culture Glutathione Hepatocytes Metabolism Nevirapine Stem cells Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry |
| title_short |
Nevirapine biotransformation insights |
| title_full |
Nevirapine biotransformation insights |
| title_fullStr |
Nevirapine biotransformation insights |
| title_full_unstemmed |
Nevirapine biotransformation insights |
| title_sort |
Nevirapine biotransformation insights |
| author |
Cipriano, Madalena |
| author_facet |
Cipriano, Madalena Pinheiro, Pedro F. Sequeira, Catarina O. Rodrigues, Joana S. Oliveira, Nuno G. Antunes, Alexandra M.M. Castro, Matilde Marques, M. Matilde Pereira, Sofia A. Miranda, Joana P. |
| author_role |
author |
| author2 |
Pinheiro, Pedro F. Sequeira, Catarina O. Rodrigues, Joana S. Oliveira, Nuno G. Antunes, Alexandra M.M. Castro, Matilde Marques, M. Matilde Pereira, Sofia A. Miranda, Joana P. |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Centro de Estudos de Doenças Crónicas (CEDOC) NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
| dc.contributor.author.fl_str_mv |
Cipriano, Madalena Pinheiro, Pedro F. Sequeira, Catarina O. Rodrigues, Joana S. Oliveira, Nuno G. Antunes, Alexandra M.M. Castro, Matilde Marques, M. Matilde Pereira, Sofia A. Miranda, Joana P. |
| dc.subject.por.fl_str_mv |
3D culture Glutathione Hepatocytes Metabolism Nevirapine Stem cells Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry |
| topic |
3D culture Glutathione Hepatocytes Metabolism Nevirapine Stem cells Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry |
| description |
Funding: This work was supported by FCT (Portugal) through the research grant PTDC/MED-TOX/29183/2017. Acknowledgments: The authors thank ECBio S.A. for providing the hnMSCs and F.A. Beland (NCTR, Jefferson, AR, USA) for the kind donation of nevirapine. FCT (UID/DTP/04138/2019, UID/QUI/00100/2019, RECI/QEQ-MED/0330/2012, SFRH/BD/144130/2019 to J.S.R., SFRH/BD/110945/2015 to P.F.P. and CEECIND/02001/2017 to A.M.M.A) are also acknowledged. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020-06-17T22:47:52Z 2020-06-01 2020-06-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10362/99536 |
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http://hdl.handle.net/10362/99536 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
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1661-6596 PURE: 18621043 https://doi.org/10.3390/ijms21113998 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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18 application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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