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A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cells

2019-06-15Journal article Restricted access
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dc.contributor.authorAssunção, Ricardo
dc.contributor.authorPinhão, Mariana
dc.contributor.authorLoureiro, Susana
dc.contributor.authorAlvito, Paula
dc.contributor.authorSilva, Maria João
dc.date.accessioned2020-04-20T19:31:13Z
dc.date.available2021-06-15T00:30:13Z
dc.date.issued2019-06-15
dc.description.abstractHumans can be exposed to a complex and variable combination of mycotoxins. After ingestion, intestinal mucosa constitutes the first biological barrier that can be exposed to high concentrations of these toxins. The present study aimed to characterize the combined cytotoxicity, genotoxicity and impact on the gastrointestinal barrier integrity of patulin (PAT, 0.7 μM to 100 μM) and ochratoxin A (OTA, 1 μM to 200 μM) mixtures in Caco-2 cells. A dose-ratio deviation was verified for cytotoxicity, implying that OTA was mainly responsible for synergism when dominant in the mixture, while this pattern was changed to antagonism for the highest PAT concentrations. Genotoxicity (comet assay) results were compatible with an interactive DNA damaging effect at the highest PAT and OTA concentrations, not clearly mediated by the formation of oxidative DNA breaks. Regarding gastrointestinal barrier integrity, a potential synergism was attained at low levels of both mycotoxins, changing to antagonism at higher doses. The present results indicate that combined mycotoxins effects may arise at the intestinal level and should not be underestimated when evaluating their risk to human health.pt_PT
dc.description.abstractHighlights: Patulin (PAT) and ochratoxin A (OTA) combined effects were studied in Caco-2 cells; To ascertain putative interactive effects conceptual mathematical models were used; Cytotoxicity data revealed a dose-ratio deviation; Genotoxicity results showed interactive DNA damaging effects; Gastrointestinal barrier integrity effects suggested a synergism at low levels of both mycotoxins.pt_PT
dc.description.sponsorshipThis research was performed under the MYCOMIX project “Exploring the toxic effects of mixtures of mycotoxins in infant food and potential health impact” (PTDC/DTP-FTO/0417/2012). Thanks are due for the financial support to CESAM (UID/AMB/50017/2019), to FCT/ MEC through national funds, and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020; and ToxOmics (UID/BIM/00009/2013), also funded by FCT, Portugal. Ricardo Assunção thanks to National Institute of Health Dr. Ricardo Jorge (BioMAN | Incentivo de Estudos de Biomonitorização Humana de Âmbito Nacional, BioMAN/DAN/01).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationToxicol Lett. 2019 Oct 1;313:120-129. doi: 10.1016/j.toxlet.2019.06.002. Epub 2019 Jun 15pt_PT
dc.identifier.doihttps://doi.org/10.1016/j.toxlet.2019.06.002pt_PT
dc.identifier.issn0378-4274
dc.identifier.urihttp://hdl.handle.net/10400.18/6464
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier/ EUROTOXpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/abs/pii/S037842741831796X?via%3Dihubpt_PT
dc.subjectSegurança Alimentarpt_PT
dc.subjectToxicologiapt_PT
dc.subjectAvaliação de Riscopt_PT
dc.subjectSaúde Humanapt_PT
dc.subjectMycotoxin Mixturespt_PT
dc.subjectGastrointestinal Toxicitypt_PT
dc.subjectGenotoxicidade Ambientalpt_PT
dc.titleA multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FDTP-FTO%2F0417%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F00009%2F2013/PT
oaire.citation.endPage129pt_PT
oaire.citation.startPage120pt_PT
oaire.citation.titleToxicology Letterspt_PT
oaire.citation.volume313pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctDe acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication7dee8a4a-7112-45ce-a8cb-8c552d7ae061
relation.isProjectOfPublicatione9cc9728-4f09-4e3a-b30d-53d4429986fb
relation.isProjectOfPublication.latestForDiscovery7dee8a4a-7112-45ce-a8cb-8c552d7ae061

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