{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:27:15Z","timestamp":1768469235905,"version":"3.49.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["435093\/2018-5"],"award-info":[{"award-number":["435093\/2018-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["Finance Code 001"],"award-info":[{"award-number":["Finance Code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017425","name":"Pr\u00f3-reitoria de Pesquisa e P\u00f3s-gradua\u00e7\u00e3o, Universidade Federal do Par\u00e1","doi-asserted-by":"crossref","award":["APC payment"],"award-info":[{"award-number":["APC payment"]}],"id":[{"id":"10.13039\/100017425","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Fluoride has become widely used in dentistry because of its effectiveness in caries control. However, evidence indicates that excessive intake interferes with the metabolic processes of different tissues. Thus, this study aimed to investigate the effects of long-term exposure to F on the parotid salivary gland of mice, from the analysis of oxidative, proteomic and genotoxic parameters.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Materials and methods<\/jats:title><jats:p>The animals received deionized water containing 0, 10 or 50 mg\/L of F, as sodium fluoride, for 60 days. After, parotid glands were collected for analysis of oxidative biochemistry, global proteomic profile, genotoxicity assessment and histopathological analyses.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>The results revealed that exposure to fluoride interfered in the biochemical homeostasis of the parotid gland, with increased levels of thiobarbituric acid reactive species and reduced glutathione in the exposed groups; as well as promoted alteration of the glandular proteomic profile in these groups, especially in structural proteins and proteins related to oxidative stress. However, genotoxic assessment demonstrated that exposure to fluoride did not interfere with DNA integrity in these concentrations and durations of exposure. Also, it was not observed histopathological alterations in parotid gland.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>Thus, our results suggest that long-term exposure to fluoride promoted modulation of the proteomic and biochemical profile in the parotid glands, without inducing damage to the genetic component. These findings reinforce the importance of rationalizing the use of fluorides to maximize their preventative effects while minimizing the environmental risks.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0261252","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T18:37:07Z","timestamp":1643308627000},"page":"e0261252","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of long-term fluoride exposure are associated with oxidative biochemistry impairment and global proteomic modulation, but not genotoxicity, in parotid glands of mice"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4489-0880","authenticated-orcid":true,"given":"Giza Hellen Nonato","family":"Miranda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leidiane","family":"Alencar de Oliveira Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo Oliveira","family":"Bittencourt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e1vio Monteiro","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Platini Caldas de Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lygia Sega","family":"Nogueira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edivaldo Herculano Corr\u00eaa","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta Chagas","family":"Monteiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline","family":"Dionizio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline Lima","family":"Leite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliano Pelim","family":"Pessan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00edlia Afonso Rabelo","family":"Buzalaf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1486-4013","authenticated-orcid":true,"given":"Rafael Rodrigues","family":"Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"issue":"7","key":"pone.0261252.ref001","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1177\/0022034519831604","article-title":"Fluoride mode of action: once there was an observant dentist","volume":"98","author":"J Ten Cate","year":"2019","journal-title":"Journal of dental research"},{"key":"pone.0261252.ref002","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.lfs.2018.02.001","article-title":"Toxic effects of fluoride on organisms","volume":"198","author":"H Zuo","year":"2018","journal-title":"Life sciences"},{"issue":"2","key":"pone.0261252.ref003","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.cbi.2010.07.011","article-title":"Molecular mechanisms of fluoride toxicity","volume":"188","author":"O Barbier","year":"2010","journal-title":"Chemico-biological interactions"},{"issue":"7","key":"pone.0261252.ref004","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1002\/ar.23569","article-title":"Overview of human salivary glands: highlights of morphology and developing processes","volume":"300","author":"F de Paula","year":"2017","journal-title":"The Anatomical Record"},{"issue":"2","key":"pone.0261252.ref005","doi-asserted-by":"crossref","first-page":"94","DOI":"10.14639\/0392-100X-1598","article-title":"Salivary biomarkers and proteomics: future diagnostic and clinical utilities","volume":"37","author":"M Castagnola","year":"2017","journal-title":"Acta Otorhinolaryngologica Italica"},{"issue":"9","key":"pone.0261252.ref006","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1177\/00220345790580091801","article-title":"Effect of dietary fluoride on rat tissue 3\u20195\u2019\u2014cyclic AMP levels.","volume":"58","author":"HS Kleiner","year":"1979","journal-title":"J Dent Res"},{"issue":"2","key":"pone.0261252.ref007","first-page":"97","article-title":"Metabolism of glycogen in submandibular glands of rats","volume":"20","author":"J Nicolau","year":"1992","journal-title":"Alteration by NaF. 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