Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell models
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , |
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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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 instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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