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

Detalhes bibliográficos
Autor(a) principal: Assunção, Ricardo
Data de Publicação: 2019
Outros Autores: Pinhão, Mariana, Loureiro, Susana, Alvito, Paula, Silva, Maria João
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6464
Resumo: Humans 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.
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spelling A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cellsSegurança AlimentarToxicologiaAvaliação de RiscoSaúde HumanaMycotoxin MixturesGastrointestinal ToxicityGenotoxicidade AmbientalHumans 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.Highlights: 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.This 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).Elsevier/ EUROTOXRepositório Científico do Instituto Nacional de SaúdeAssunção, RicardoPinhão, MarianaLoureiro, SusanaAlvito, PaulaSilva, Maria João2021-06-15T00:30:13Z2019-06-152019-06-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6464engToxicol Lett. 2019 Oct 1;313:120-129. doi: 10.1016/j.toxlet.2019.06.002. Epub 2019 Jun 150378-4274https://doi.org/10.1016/j.toxlet.2019.06.002info: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:RCAAP2023-07-20T15:41:26Zoai:repositorio.insa.pt:10400.18/6464Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:41:07.913759Repositório 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 A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cells
title A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cells
spellingShingle A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cells
Assunção, Ricardo
Segurança Alimentar
Toxicologia
Avaliação de Risco
Saúde Humana
Mycotoxin Mixtures
Gastrointestinal Toxicity
Genotoxicidade Ambiental
title_short A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cells
title_full A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cells
title_fullStr A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cells
title_full_unstemmed A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cells
title_sort A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cells
author Assunção, Ricardo
author_facet Assunção, Ricardo
Pinhão, Mariana
Loureiro, Susana
Alvito, Paula
Silva, Maria João
author_role author
author2 Pinhão, Mariana
Loureiro, Susana
Alvito, Paula
Silva, Maria João
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Assunção, Ricardo
Pinhão, Mariana
Loureiro, Susana
Alvito, Paula
Silva, Maria João
dc.subject.por.fl_str_mv Segurança Alimentar
Toxicologia
Avaliação de Risco
Saúde Humana
Mycotoxin Mixtures
Gastrointestinal Toxicity
Genotoxicidade Ambiental
topic Segurança Alimentar
Toxicologia
Avaliação de Risco
Saúde Humana
Mycotoxin Mixtures
Gastrointestinal Toxicity
Genotoxicidade Ambiental
description Humans 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.
publishDate 2019
dc.date.none.fl_str_mv 2019-06-15
2019-06-15T00:00:00Z
2021-06-15T00:30:13Z
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 http://hdl.handle.net/10400.18/6464
url http://hdl.handle.net/10400.18/6464
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Toxicol Lett. 2019 Oct 1;313:120-129. doi: 10.1016/j.toxlet.2019.06.002. Epub 2019 Jun 15
0378-4274
https://doi.org/10.1016/j.toxlet.2019.06.002
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.publisher.none.fl_str_mv Elsevier/ EUROTOX
publisher.none.fl_str_mv Elsevier/ EUROTOX
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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