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

Detalhes bibliográficos
Autor(a) principal: Pinhão, Mariana
Data de Publicação: 2020
Outros Autores: Tavares, Ana Maria, Loureiro, Susana, Louro, Henriqueta, 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/10400.18/7358
Resumo: Food 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.
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spelling Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell modelsMycotoxinsMixtures ToxicityFumonisin B(1)GenotoxicityEnvironmental GenotoxicityInteractive EffectsFood SafetyLiver and Kidney ToxicityOchratoxin AGenotoxicidade AmbientalSegurança AlimentarFood 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.Highlights: 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.Funded 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)Elsevier/ European Society for Toxicology in VitroRepositório Científico do Instituto Nacional de SaúdePinhão, MarianaTavares, Ana MariaLoureiro, SusanaLouro, HenriquetaAlvito, PaulaSilva, Maria João2021-03-07T16:59:46Z2020-102020-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/7358engToxicol In Vitro. 2020 Oct;68:104949. doi: 10.1016/j.tiv.2020.104949. Epub 2020 Jul 24.0887-233310.1016/j.tiv.2020.104949info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:41:56Zoai:repositorio.insa.pt:10400.18/7358Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:41:58.507440Repositório 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 Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell models
title Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell models
spellingShingle Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell models
Pinhão, Mariana
Mycotoxins
Mixtures Toxicity
Fumonisin B(1)
Genotoxicity
Environmental Genotoxicity
Interactive Effects
Food Safety
Liver and Kidney Toxicity
Ochratoxin A
Genotoxicidade Ambiental
Segurança Alimentar
title_short Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell models
title_full Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell models
title_fullStr Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell models
title_full_unstemmed Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell models
title_sort Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell models
author Pinhão, Mariana
author_facet Pinhão, Mariana
Tavares, Ana Maria
Loureiro, Susana
Louro, Henriqueta
Alvito, Paula
Silva, Maria João
author_role author
author2 Tavares, Ana Maria
Loureiro, Susana
Louro, Henriqueta
Alvito, Paula
Silva, Maria João
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Pinhão, Mariana
Tavares, Ana Maria
Loureiro, Susana
Louro, Henriqueta
Alvito, Paula
Silva, Maria João
dc.subject.por.fl_str_mv Mycotoxins
Mixtures Toxicity
Fumonisin B(1)
Genotoxicity
Environmental Genotoxicity
Interactive Effects
Food Safety
Liver and Kidney Toxicity
Ochratoxin A
Genotoxicidade Ambiental
Segurança Alimentar
topic Mycotoxins
Mixtures Toxicity
Fumonisin B(1)
Genotoxicity
Environmental Genotoxicity
Interactive Effects
Food Safety
Liver and Kidney Toxicity
Ochratoxin A
Genotoxicidade Ambiental
Segurança Alimentar
description Food 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.
publishDate 2020
dc.date.none.fl_str_mv 2020-10
2020-10-01T00:00:00Z
2021-03-07T16:59:46Z
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/10400.18/7358
url http://hdl.handle.net/10400.18/7358
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Toxicol In Vitro. 2020 Oct;68:104949. doi: 10.1016/j.tiv.2020.104949. Epub 2020 Jul 24.
0887-2333
10.1016/j.tiv.2020.104949
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier/ European Society for Toxicology in Vitro
publisher.none.fl_str_mv Elsevier/ European Society for Toxicology in Vitro
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
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instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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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
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