Zebrafish larvae are a suitable model to investigate the metabolic phenotype of drug-induced renal tubular injury
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | https://doi.org/10.3389/fphar.2018.01193 |
Resumo: | This work was supported by the Calouste Gulbenkian Foundation, Gulbenkian Professorship 121986, 2012; the Foundation for Science and Technology of Portugal, mobility grant SFRH/BSAB/114291/2016 (to JM); and iNOVA4Health - UID/Multi/04462/2013, a program financially supported by Fundacao para a Ciencia e Tecnologia/Ministerio da Educacao e Ciencia, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. |
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Zebrafish larvae are a suitable model to investigate the metabolic phenotype of drug-induced renal tubular injuryKidney injury biomarkersMetabolomicsMitochondriaRenal tubular toxicityTranslational modelsZebrafishPharmacologyPharmacology (medical)This work was supported by the Calouste Gulbenkian Foundation, Gulbenkian Professorship 121986, 2012; the Foundation for Science and Technology of Portugal, mobility grant SFRH/BSAB/114291/2016 (to JM); and iNOVA4Health - UID/Multi/04462/2013, a program financially supported by Fundacao para a Ciencia e Tecnologia/Ministerio da Educacao e Ciencia, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement.Prevention and treatment of drug-induced renal injury (DIRI) rely on the availability of sensitive and specific biomarkers of early kidney injury and predictive animal models of human pathophysiology. This study aimed to evaluate the potential of zebrafish larvae as translational model in metabolic profiling of DIRI. Zebrafish larvae were exposed to the lethal concentration for 10% of the larvae (LC10) or ½ LC10 of gentamicin, paracetamol and tenofovir as tenofovir disoproxil fumarate (TDF) and tenofovir (TFV). Metabolites were extracted from whole larvae and analyzed by liquid chromatography-mass spectrometry. Principal component analysis showed that drug exposition to the LC10 of paracetamol, TFV, and TDF was the main source of the variance of the data. To identify the metabolites responsible for the toxic effects of the drugs, partial least squares discriminant analyses were built between the LC10 and ½ LC10 for each drug. Features with variable importance in projection> 1.0 were selected and Venn diagrams were built to differentiate between the common and drug specific metabolites of DIRI. Creatine, tyrosine, glutamine, guanosine, hypoxanthine were identified as common metabolites, adenosine and tryptophan as paracetamol-specific and xanthine and oxidized glutathione as tenofovir-specific. Those metabolic changes can be associated with alterations in energy metabolism, xenobiotic detoxification and protein catabolism, all described in the human pathophysiology of DIRI. Thus, zebrafish proved to be a suitable model to characterize the metabolic changes associated with DIRI. This information can be useful to early diagnose DIRI and to improve our knowledge on the mechanisms of DIRI.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNMorello, JuditDerks, Rico J.E.Lopes, Susana S.Steenvoorden, EvelyneMonteiro, Emilia C.Mayboroda, Oleg A.Pereira, Sofia A.2018-11-05T23:29:14Z2018-10-162018-10-16T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.3389/fphar.2018.01193eng1663-9812PURE: 6159928http://www.scopus.com/inward/record.url?scp=85055245721&partnerID=8YFLogxKhttps://doi.org/10.3389/fphar.2018.01193info: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:RCAAP2024-03-11T04:25:31Zoai:run.unl.pt:10362/50860Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:32:20.813864Repositório 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 |
Zebrafish larvae are a suitable model to investigate the metabolic phenotype of drug-induced renal tubular injury |
| title |
Zebrafish larvae are a suitable model to investigate the metabolic phenotype of drug-induced renal tubular injury |
| spellingShingle |
Zebrafish larvae are a suitable model to investigate the metabolic phenotype of drug-induced renal tubular injury Morello, Judit Kidney injury biomarkers Metabolomics Mitochondria Renal tubular toxicity Translational models Zebrafish Pharmacology Pharmacology (medical) |
| title_short |
Zebrafish larvae are a suitable model to investigate the metabolic phenotype of drug-induced renal tubular injury |
| title_full |
Zebrafish larvae are a suitable model to investigate the metabolic phenotype of drug-induced renal tubular injury |
| title_fullStr |
Zebrafish larvae are a suitable model to investigate the metabolic phenotype of drug-induced renal tubular injury |
| title_full_unstemmed |
Zebrafish larvae are a suitable model to investigate the metabolic phenotype of drug-induced renal tubular injury |
| title_sort |
Zebrafish larvae are a suitable model to investigate the metabolic phenotype of drug-induced renal tubular injury |
| author |
Morello, Judit |
| author_facet |
Morello, Judit Derks, Rico J.E. Lopes, Susana S. Steenvoorden, Evelyne Monteiro, Emilia C. Mayboroda, Oleg A. Pereira, Sofia A. |
| author_role |
author |
| author2 |
Derks, Rico J.E. Lopes, Susana S. Steenvoorden, Evelyne Monteiro, Emilia C. Mayboroda, Oleg A. Pereira, Sofia A. |
| author2_role |
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 |
Morello, Judit Derks, Rico J.E. Lopes, Susana S. Steenvoorden, Evelyne Monteiro, Emilia C. Mayboroda, Oleg A. Pereira, Sofia A. |
| dc.subject.por.fl_str_mv |
Kidney injury biomarkers Metabolomics Mitochondria Renal tubular toxicity Translational models Zebrafish Pharmacology Pharmacology (medical) |
| topic |
Kidney injury biomarkers Metabolomics Mitochondria Renal tubular toxicity Translational models Zebrafish Pharmacology Pharmacology (medical) |
| description |
This work was supported by the Calouste Gulbenkian Foundation, Gulbenkian Professorship 121986, 2012; the Foundation for Science and Technology of Portugal, mobility grant SFRH/BSAB/114291/2016 (to JM); and iNOVA4Health - UID/Multi/04462/2013, a program financially supported by Fundacao para a Ciencia e Tecnologia/Ministerio da Educacao e Ciencia, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018-11-05T23:29:14Z 2018-10-16 2018-10-16T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
https://doi.org/10.3389/fphar.2018.01193 |
| url |
https://doi.org/10.3389/fphar.2018.01193 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1663-9812 PURE: 6159928 http://www.scopus.com/inward/record.url?scp=85055245721&partnerID=8YFLogxK https://doi.org/10.3389/fphar.2018.01193 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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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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