Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.cbi.2017.01.005 http://hdl.handle.net/11449/169386 |
Resumo: | Studies focusing on possible genotoxic effects of excess fluoride are contradictory and inconclusive. Currently, studies have reported a probable link to oxidative stress, DNA damage and apoptosis induced by fluoride in rat hepatocytes. We developed an in vivo study administering three doses of fluoride by gavage given to rats for 60 day. Micronucleus test was applied to investigate genotoxic potential of fluoride. The TUNEL method determined DNA fragmentation and apoptosis. Biochemical parameters to investigate mitochondrial swelling and oxidative stress. Semi-quantitative RT-PCR and immunostaining to determine mRNA and protein expression of antioxidant enzymes. Analyses of the hepatic function and morphology were performed. Our results revealed the genotoxic potential of fluoride but did not confirm mitochondrial swelling nor an increase of positive TUNEL labelling induced by fluoride, indicating absence of apoptosis. Oxidative stress induction was confirmed and is probably associated to DNA damage. Cell death events such as empty nuclear spaces, cytoplasm degeneration, nuclear pyknosis, karyorrhexis and karyorrhexis followed by karyolysis were observed. Hepatic function did not appear to be significantly modified makes no evidence of necrosis and suggesting other cell death pathway, the autophagic. In conclusion, prolonged fluoride intake at chosen concentrations caused imbalance of the cellular oxidative state, affected DNA and disrupted cellular homeostasis. It is recommended that fluoride supplementation requires a fresh consideration in light of the current study. |
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Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposureCell deathHepatic injuryMicronucleiMitochondrial swellingOxidative stressStudies focusing on possible genotoxic effects of excess fluoride are contradictory and inconclusive. Currently, studies have reported a probable link to oxidative stress, DNA damage and apoptosis induced by fluoride in rat hepatocytes. We developed an in vivo study administering three doses of fluoride by gavage given to rats for 60 day. Micronucleus test was applied to investigate genotoxic potential of fluoride. The TUNEL method determined DNA fragmentation and apoptosis. Biochemical parameters to investigate mitochondrial swelling and oxidative stress. Semi-quantitative RT-PCR and immunostaining to determine mRNA and protein expression of antioxidant enzymes. Analyses of the hepatic function and morphology were performed. Our results revealed the genotoxic potential of fluoride but did not confirm mitochondrial swelling nor an increase of positive TUNEL labelling induced by fluoride, indicating absence of apoptosis. Oxidative stress induction was confirmed and is probably associated to DNA damage. Cell death events such as empty nuclear spaces, cytoplasm degeneration, nuclear pyknosis, karyorrhexis and karyorrhexis followed by karyolysis were observed. Hepatic function did not appear to be significantly modified makes no evidence of necrosis and suggesting other cell death pathway, the autophagic. In conclusion, prolonged fluoride intake at chosen concentrations caused imbalance of the cellular oxidative state, affected DNA and disrupted cellular homeostasis. It is recommended that fluoride supplementation requires a fresh consideration in light of the current study.São Paulo State University (UNESP) Department of Biology Institute of Biosciences, Avenida 24-A, nº 1515, Bela VistaHeath Sciences Nucleus Hermínio Ometto University Center UNIARARAS Jd. Universitário, Avenida Dr. Maximiliano Barutto, nº 500Structural and Functional Biology Laboratory (LABEF) Federal University of São Carlos – UFSCAR, Rodovia João Leme dos Santos, Km 110 - SP-264Graduate Program in Biomedical Sciences Hermínio Ometto University Center UNIARARAS Jd. Universitário, Avenida Dr. Maximiliano Barutto, nº 500Reproductive Biology Laboratory Structural and Functional Biology Department State University of Campinas – UNICAMP, CP. 6109São Paulo State University (UNESP) Department of Biology Institute of Biosciences, Avenida 24-A, nº 1515, Bela VistaUniversidade Estadual Paulista (Unesp)Jd. UniversitárioUniversidade Federal de São Carlos (UFSCar)Universidade Estadual de Campinas (UNICAMP)Campos-Pereira, F. D. [UNESP]Lopes-Aguiar, L.Renosto, F. L.Nogueira, G. A.S.Costa, E. F.D.Barbieri Pulz, R.Silva-Zacarin, E. C.M.Oliveira, C. A.Pigoso, A. A.Severi-Aguiar, G. D.C.2018-12-11T16:45:38Z2018-12-11T16:45:38Z2017-02-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article25-33application/pdfhttp://dx.doi.org/10.1016/j.cbi.2017.01.005Chemico-Biological Interactions, v. 264, p. 25-33.1872-77860009-2797http://hdl.handle.net/11449/16938610.1016/j.cbi.2017.01.0052-s2.0-850100320642-s2.0-85010032064.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengChemico-Biological Interactions1,033info:eu-repo/semantics/openAccess2024-01-09T06:27:06Zoai:repositorio.unesp.br:11449/169386Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:30:28.306559Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure |
title |
Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure |
spellingShingle |
Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure Campos-Pereira, F. D. [UNESP] Cell death Hepatic injury Micronuclei Mitochondrial swelling Oxidative stress |
title_short |
Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure |
title_full |
Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure |
title_fullStr |
Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure |
title_full_unstemmed |
Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure |
title_sort |
Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure |
author |
Campos-Pereira, F. D. [UNESP] |
author_facet |
Campos-Pereira, F. D. [UNESP] Lopes-Aguiar, L. Renosto, F. L. Nogueira, G. A.S. Costa, E. F.D. Barbieri Pulz, R. Silva-Zacarin, E. C.M. Oliveira, C. A. Pigoso, A. A. Severi-Aguiar, G. D.C. |
author_role |
author |
author2 |
Lopes-Aguiar, L. Renosto, F. L. Nogueira, G. A.S. Costa, E. F.D. Barbieri Pulz, R. Silva-Zacarin, E. C.M. Oliveira, C. A. Pigoso, A. A. Severi-Aguiar, G. D.C. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Jd. Universitário Universidade Federal de São Carlos (UFSCar) Universidade Estadual de Campinas (UNICAMP) |
dc.contributor.author.fl_str_mv |
Campos-Pereira, F. D. [UNESP] Lopes-Aguiar, L. Renosto, F. L. Nogueira, G. A.S. Costa, E. F.D. Barbieri Pulz, R. Silva-Zacarin, E. C.M. Oliveira, C. A. Pigoso, A. A. Severi-Aguiar, G. D.C. |
dc.subject.por.fl_str_mv |
Cell death Hepatic injury Micronuclei Mitochondrial swelling Oxidative stress |
topic |
Cell death Hepatic injury Micronuclei Mitochondrial swelling Oxidative stress |
description |
Studies focusing on possible genotoxic effects of excess fluoride are contradictory and inconclusive. Currently, studies have reported a probable link to oxidative stress, DNA damage and apoptosis induced by fluoride in rat hepatocytes. We developed an in vivo study administering three doses of fluoride by gavage given to rats for 60 day. Micronucleus test was applied to investigate genotoxic potential of fluoride. The TUNEL method determined DNA fragmentation and apoptosis. Biochemical parameters to investigate mitochondrial swelling and oxidative stress. Semi-quantitative RT-PCR and immunostaining to determine mRNA and protein expression of antioxidant enzymes. Analyses of the hepatic function and morphology were performed. Our results revealed the genotoxic potential of fluoride but did not confirm mitochondrial swelling nor an increase of positive TUNEL labelling induced by fluoride, indicating absence of apoptosis. Oxidative stress induction was confirmed and is probably associated to DNA damage. Cell death events such as empty nuclear spaces, cytoplasm degeneration, nuclear pyknosis, karyorrhexis and karyorrhexis followed by karyolysis were observed. Hepatic function did not appear to be significantly modified makes no evidence of necrosis and suggesting other cell death pathway, the autophagic. In conclusion, prolonged fluoride intake at chosen concentrations caused imbalance of the cellular oxidative state, affected DNA and disrupted cellular homeostasis. It is recommended that fluoride supplementation requires a fresh consideration in light of the current study. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-02-25 2018-12-11T16:45:38Z 2018-12-11T16:45:38Z |
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://dx.doi.org/10.1016/j.cbi.2017.01.005 Chemico-Biological Interactions, v. 264, p. 25-33. 1872-7786 0009-2797 http://hdl.handle.net/11449/169386 10.1016/j.cbi.2017.01.005 2-s2.0-85010032064 2-s2.0-85010032064.pdf |
url |
http://dx.doi.org/10.1016/j.cbi.2017.01.005 http://hdl.handle.net/11449/169386 |
identifier_str_mv |
Chemico-Biological Interactions, v. 264, p. 25-33. 1872-7786 0009-2797 10.1016/j.cbi.2017.01.005 2-s2.0-85010032064 2-s2.0-85010032064.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Chemico-Biological Interactions 1,033 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
25-33 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808129433612058624 |