Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure

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dc.contributor.authorCampos-Pereira, F. D. [UNESP]
dc.contributor.authorLopes-Aguiar, L.
dc.contributor.authorRenosto, F. L.
dc.contributor.authorNogueira, G. A.S.
dc.contributor.authorCosta, E. F.D.
dc.contributor.authorBarbieri Pulz, R.
dc.contributor.authorSilva-Zacarin, E. C.M.
dc.contributor.authorOliveira, C. A.
dc.contributor.authorPigoso, A. A.
dc.contributor.authorSeveri-Aguiar, G. D.C.
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionJd. Universitário
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.date.accessioned2018-12-11T16:45:38Z
dc.date.available2018-12-11T16:45:38Z
dc.date.issued2017-02-25
dc.description.abstractStudies 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.en
dc.description.affiliationSão Paulo State University (UNESP) Department of Biology Institute of Biosciences, Avenida 24-A, nº 1515, Bela Vista
dc.description.affiliationHeath Sciences Nucleus Hermínio Ometto University Center UNIARARAS Jd. Universitário, Avenida Dr. Maximiliano Barutto, nº 500
dc.description.affiliationStructural and Functional Biology Laboratory (LABEF) Federal University of São Carlos – UFSCAR, Rodovia João Leme dos Santos, Km 110 - SP-264
dc.description.affiliationGraduate Program in Biomedical Sciences Hermínio Ometto University Center UNIARARAS Jd. Universitário, Avenida Dr. Maximiliano Barutto, nº 500
dc.description.affiliationReproductive Biology Laboratory Structural and Functional Biology Department State University of Campinas – UNICAMP, CP. 6109
dc.description.affiliationUnespSão Paulo State University (UNESP) Department of Biology Institute of Biosciences, Avenida 24-A, nº 1515, Bela Vista
dc.format.extent25-33
dc.identifierhttp://dx.doi.org/10.1016/j.cbi.2017.01.005
dc.identifier.citationChemico-Biological Interactions, v. 264, p. 25-33.
dc.identifier.doi10.1016/j.cbi.2017.01.005
dc.identifier.file2-s2.0-85010032064.pdf
dc.identifier.issn1872-7786
dc.identifier.issn0009-2797
dc.identifier.scopus2-s2.0-85010032064
dc.identifier.urihttp://hdl.handle.net/11449/169386
dc.language.isoeng
dc.relation.ispartofChemico-Biological Interactions
dc.relation.ispartofsjr1,033
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectCell death
dc.subjectHepatic injury
dc.subjectMicronuclei
dc.subjectMitochondrial swelling
dc.subjectOxidative stress
dc.titleGenotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposureen
dc.typeArtigo
unesp.author.orcid0000-0002-7767-3356[1]
unesp.author.orcid0000-0003-3321-3830[10]

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