Zebrafish larvae are a suitable model to investigate the metabolic phenotype of drug-induced renal tubular injury

Bibliographic Details
Main Author: Morello, Judit
Publication Date: 2018
Other Authors: Derks, Rico J.E., Lopes, Susana S., Steenvoorden, Evelyne, Monteiro, Emilia C., Mayboroda, Oleg A., Pereira, Sofia A.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: https://doi.org/10.3389/fphar.2018.01193
Summary: 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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spelling 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:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T17:35:22Zoai:run.unl.pt:10362/50860Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:06:16.279859Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
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
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str 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
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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