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Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell models

dc.contributor.authorPinhão, Mariana
dc.contributor.authorTavares, Ana Maria
dc.contributor.authorLoureiro, Susana
dc.contributor.authorLouro, Henriqueta
dc.contributor.authorAlvito, Paula
dc.contributor.authorSilva, Maria João
dc.date.accessioned2021-03-07T16:59:46Z
dc.date.available2021-03-07T16:59:46Z
dc.date.issued2020-10
dc.description.abstractFood products can be contaminated by several fungi species and each species may produce different mycotoxins, leading to human combined exposure. Although predictions about the joint toxic effects of mycotoxins can be made from their individual toxicities, experimental data is still limited to allow a reliable hazard assessment. Thus, this study aimed to characterize the combined cytotoxic and genotoxic effects of ochratoxin A (OTA) and fumonisin B1 (FB1) in cell lines representative of their target organs, kidney and liver. Interactions were ascertained using mathematical extensions to the reference models of concentration addition and independent action. Cytotoxicity (MTT assay) data modeling revealed a synergistic pattern for low doses of both FB1 and OTA shifting to antagonism at higher concentration levels, irrespectively of the reference model applied. Concerning genotoxicity assessment, neither OTA nor FB1, individually or in combination, induced a prominent increase in DNA damage (comet assay) or oxidative DNA damage (FPG-comet assay). In conclusion, this study revealed a synergistic cytotoxic effect for OTA and FB1 at low concentration levels. Given that human co-exposure to these two mycotoxins is probable to occur at low doses, these results raise concerns regarding their potential health outcomes that seem to differ from those predicted by an additive model.pt_PT
dc.description.abstractHighlights: Ochratoxin A significantly induced cytotoxicity in HK-2 and HepG2 cells; Fumonisin B1 did not induce cytotoxicity in HK-2 nor HepG2 cells; Joint effects of both toxins were assessed through the Concentration Addition and Independent Action mathematical models; Synergistic cytotoxic effects were observed at low ochratoxin A and fumonisin B1 concentrations in both cell models.pt_PT
dc.description.sponsorshipFunded by FCT/MCTES through national funds attributed to earlyMyco (PTDC/MED-TOX/28762/2017), CESAM (UIDP/50017/ 2020 + UIDB/50017/2020), and ToxOmics (UID/BIM/00009/2019)pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationToxicol In Vitro. 2020 Oct;68:104949. doi: 10.1016/j.tiv.2020.104949. Epub 2020 Jul 24.pt_PT
dc.identifier.doi10.1016/j.tiv.2020.104949pt_PT
dc.identifier.issn0887-2333
dc.identifier.urihttp://hdl.handle.net/10400.18/7358
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier/ European Society for Toxicology in Vitropt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/abs/pii/S0887233320304999?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectMycotoxinspt_PT
dc.subjectMixtures Toxicitypt_PT
dc.subjectFumonisin B(1)pt_PT
dc.subjectGenotoxicitypt_PT
dc.subjectEnvironmental Genotoxicitypt_PT
dc.subjectInteractive Effectspt_PT
dc.subjectFood Safetypt_PT
dc.subjectLiver and Kidney Toxicitypt_PT
dc.subjectOchratoxin Apt_PT
dc.subjectGenotoxicidade Ambientalpt_PT
dc.subjectSegurança Alimentarpt_PT
dc.titleCombined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell modelspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F00009%2F2013/PT (2019)
oaire.citation.startPage104949pt_PT
oaire.citation.titleToxicology in Vitropt_PT
oaire.citation.volume68pt_PT
oaire.fundingStream5876
person.familyNameLouro
person.familyNameSilva
person.givenNameHenriqueta
person.givenNameMaria Joao
person.identifier157627
person.identifier.ciencia-id721D-2BB1-7DB1
person.identifier.ciencia-id7710-643D-97A3
person.identifier.orcid0000-0001-9744-7332
person.identifier.orcid0000-0002-6060-0716
person.identifier.scopus-author-id6507971479
person.identifier.scopus-author-id55944437600
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication2361a951-8b9a-4b90-92d6-f6384003a242
relation.isAuthorOfPublicationa7763685-7c34-468d-b958-9dd0aca66db4
relation.isAuthorOfPublication.latestForDiscoverya7763685-7c34-468d-b958-9dd0aca66db4
relation.isProjectOfPublicationa028cb4d-a824-48dc-b77d-a52ffa9e889b
relation.isProjectOfPublication.latestForDiscoverya028cb4d-a824-48dc-b77d-a52ffa9e889b

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