Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: an integrative approach of complementary endpoints
Autor(a) principal: | |
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Data de Publicação: | 2015 |
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/10400.18/3430 |
Resumo: | Ochratoxin A (OTA) is a well-known nephrotoxic and potential carcinogenic agent but no consensus about the molecular mechanisms underlying its deleterious effects has been reached yet. The aim of this study is to integrate several endpoints concerning OTA-induced toxicological effects in Vero kidney cells in order to obtain additional mechanistic data, especially regarding the influence of reactive oxygen species (ROS). One innovative aspect of this work is the use of the superoxide dismutase mimic (SODm) MnTnHex-2-PyP as a mechanistic tool to clarify the involvement of oxidative stress in OTA toxicity. The results showed concentration and time-dependent cytotoxic effects of OTA (crystal violet, neutral red and LDH leakage assays). While the SODm mildly increased cell viability, trolox and ascorbic acid had no effect with regards to this endpoint. OTA induced micronuclei formation. Using the FPG modified comet assay, OTA modestly increased the % of DNA in tail, revealing the presence of oxidative DNA lesions. This mycotoxin increased apoptosis, which was attenuated by SODm. In addition, the SODm decreased the ROS accumulation observed in DHE assay. Taken together, our data suggest that ROS partially contribute to the cytotoxicity and genotoxicity of OTA, although other mechanisms may be relevant in OTA-induced deleterious effects. |
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Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: an integrative approach of complementary endpointsGenotoxicidade AmbientalGenotoxicityOchratoxin ACytotoxicityReactive Oxygen SpeciesAntioxidantsMnTnHex-2-PyPOchratoxin A (OTA) is a well-known nephrotoxic and potential carcinogenic agent but no consensus about the molecular mechanisms underlying its deleterious effects has been reached yet. The aim of this study is to integrate several endpoints concerning OTA-induced toxicological effects in Vero kidney cells in order to obtain additional mechanistic data, especially regarding the influence of reactive oxygen species (ROS). One innovative aspect of this work is the use of the superoxide dismutase mimic (SODm) MnTnHex-2-PyP as a mechanistic tool to clarify the involvement of oxidative stress in OTA toxicity. The results showed concentration and time-dependent cytotoxic effects of OTA (crystal violet, neutral red and LDH leakage assays). While the SODm mildly increased cell viability, trolox and ascorbic acid had no effect with regards to this endpoint. OTA induced micronuclei formation. Using the FPG modified comet assay, OTA modestly increased the % of DNA in tail, revealing the presence of oxidative DNA lesions. This mycotoxin increased apoptosis, which was attenuated by SODm. In addition, the SODm decreased the ROS accumulation observed in DHE assay. Taken together, our data suggest that ROS partially contribute to the cytotoxicity and genotoxicity of OTA, although other mechanisms may be relevant in OTA-induced deleterious effects.The current work was funded, in part, by iMed.ULisboa (UID/DTP/04138/2013), research grants SFRH/BPD/96719/2013 to JPM and SFRH/BD/70293/2010 to PSG from Fundação para a Ciência e a Tecnologia, Portugal, by European Cooperation in Science and Research (COST Action BM1203/EU-ROS) and by IBH general research funds.Elsevier/ PergamonRepositório Científico do Instituto Nacional de SaúdeCosta, J.G.Saraiva, N.Guerreiro, P.S.Louro, HenriquetaSilva, Maria JoãoMiranda, J.P.Castro, M.Batinic-Haberle, I.Fernandes, A.S.Oliveira, N.G.2017-11-25T01:30:08Z2015-12-022015-12-02T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10400.18/3430engFood Chem Toxicol. 2016 Jan;87:65-76. doi: 10.1016/j.fct.2015.11.018. Epub 2015 Dec 20278-691510.1016/j.fct.2015.11.018.info: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:RCAAP2023-07-20T15:39:44Zoai:repositorio.insa.pt:10400.18/3430Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:38:13.970479Repositório 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 |
Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: an integrative approach of complementary endpoints |
title |
Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: an integrative approach of complementary endpoints |
spellingShingle |
Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: an integrative approach of complementary endpoints Costa, J.G. Genotoxicidade Ambiental Genotoxicity Ochratoxin A Cytotoxicity Reactive Oxygen Species Antioxidants MnTnHex-2-PyP |
title_short |
Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: an integrative approach of complementary endpoints |
title_full |
Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: an integrative approach of complementary endpoints |
title_fullStr |
Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: an integrative approach of complementary endpoints |
title_full_unstemmed |
Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: an integrative approach of complementary endpoints |
title_sort |
Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: an integrative approach of complementary endpoints |
author |
Costa, J.G. |
author_facet |
Costa, J.G. Saraiva, N. Guerreiro, P.S. Louro, Henriqueta Silva, Maria João Miranda, J.P. Castro, M. Batinic-Haberle, I. Fernandes, A.S. Oliveira, N.G. |
author_role |
author |
author2 |
Saraiva, N. Guerreiro, P.S. Louro, Henriqueta Silva, Maria João Miranda, J.P. Castro, M. Batinic-Haberle, I. Fernandes, A.S. Oliveira, N.G. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Costa, J.G. Saraiva, N. Guerreiro, P.S. Louro, Henriqueta Silva, Maria João Miranda, J.P. Castro, M. Batinic-Haberle, I. Fernandes, A.S. Oliveira, N.G. |
dc.subject.por.fl_str_mv |
Genotoxicidade Ambiental Genotoxicity Ochratoxin A Cytotoxicity Reactive Oxygen Species Antioxidants MnTnHex-2-PyP |
topic |
Genotoxicidade Ambiental Genotoxicity Ochratoxin A Cytotoxicity Reactive Oxygen Species Antioxidants MnTnHex-2-PyP |
description |
Ochratoxin A (OTA) is a well-known nephrotoxic and potential carcinogenic agent but no consensus about the molecular mechanisms underlying its deleterious effects has been reached yet. The aim of this study is to integrate several endpoints concerning OTA-induced toxicological effects in Vero kidney cells in order to obtain additional mechanistic data, especially regarding the influence of reactive oxygen species (ROS). One innovative aspect of this work is the use of the superoxide dismutase mimic (SODm) MnTnHex-2-PyP as a mechanistic tool to clarify the involvement of oxidative stress in OTA toxicity. The results showed concentration and time-dependent cytotoxic effects of OTA (crystal violet, neutral red and LDH leakage assays). While the SODm mildly increased cell viability, trolox and ascorbic acid had no effect with regards to this endpoint. OTA induced micronuclei formation. Using the FPG modified comet assay, OTA modestly increased the % of DNA in tail, revealing the presence of oxidative DNA lesions. This mycotoxin increased apoptosis, which was attenuated by SODm. In addition, the SODm decreased the ROS accumulation observed in DHE assay. Taken together, our data suggest that ROS partially contribute to the cytotoxicity and genotoxicity of OTA, although other mechanisms may be relevant in OTA-induced deleterious effects. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-12-02 2015-12-02T00:00:00Z 2017-11-25T01:30:08Z |
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/10400.18/3430 |
url |
http://hdl.handle.net/10400.18/3430 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Food Chem Toxicol. 2016 Jan;87:65-76. doi: 10.1016/j.fct.2015.11.018. Epub 2015 Dec 2 0278-6915 10.1016/j.fct.2015.11.018. |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
eu_rights_str_mv |
embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier/ Pergamon |
publisher.none.fl_str_mv |
Elsevier/ Pergamon |
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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1799132118994911232 |