{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:19:55Z","timestamp":1789445995816,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T00:00:00Z","timestamp":1537315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008532","name":"Universidade Federal do Rio Grande do Norte","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008532","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2018,11]]},"abstract":"\n Background<\/jats:title>\n \n The aim of this study was to evaluate the effect of olmesartan medoxomil (Olme), an angiotensin\n II<\/jats:styled-content>\n receptor antagonist, on oral mucositis (\n OM<\/jats:styled-content>\n ) experimental model.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Oral mucositis was induced in hamsters with 5\u2010fluorouracil (5\u2010\n FU<\/jats:styled-content>\n ; 60\u00a0mg\/kg day 1 and 40\u00a0mg\/kg day 2). Animals (n\u00a0=\u00a010\/group) were pretreated with oral Olme (1, 5, or 10\u00a0mg\/kg) or vehicle 30\u00a0minutes before 5\u2010\n FU<\/jats:styled-content>\n injection and daily, until day 10. Cheek pouch samples were subjected to histopathological and immunostaining analysis of\n IL<\/jats:styled-content>\n \u20101\u03b2,\n TNF<\/jats:styled-content>\n \u2010\u03b1,\n IL<\/jats:styled-content>\n \u201010,\n TGF<\/jats:styled-content>\n \u2010\u03b2, macrophage migration inhibitory factor (\n MIF<\/jats:styled-content>\n ),\n SOD<\/jats:styled-content>\n ,\n MMP<\/jats:styled-content>\n \u20102 and\n FGF<\/jats:styled-content>\n \u20102. In addition,\n IL<\/jats:styled-content>\n \u20101\u03b2 and\n TNF<\/jats:styled-content>\n \u2010\u03b1 levels were evaluated by\n ELISA<\/jats:styled-content>\n . Myeloperoxidase activity (\n MPO<\/jats:styled-content>\n ), glutathione (\n GSH<\/jats:styled-content>\n ) and malondialdehyde (\n MDA<\/jats:styled-content>\n ) levels were investigated by spectroscopic\n UV<\/jats:styled-content>\n \/\n VIS<\/jats:styled-content>\n analysis. Reverse transcriptase polymerase chain reactions (\n RT<\/jats:styled-content>\n \u2010\n PCR<\/jats:styled-content>\n s) were used to quantify the expression of\n \n IL<\/jats:styled-content>\n \u20101\n <\/jats:italic>\n \u03b2\n \n ,\n TNF<\/jats:styled-content>\n \u2010\n <\/jats:italic>\n \u03b1\n \n ,\n NF<\/jats:styled-content>\n \u2010\n <\/jats:italic>\n \u03ba\n Bp65<\/jats:italic>\n ,\n \n MKP<\/jats:styled-content>\n 1\n <\/jats:italic>\n and\n \n ACE<\/jats:styled-content>\n 2\n <\/jats:italic>\n . Inducible nitric oxide synthase (\n iNOS<\/jats:styled-content>\n ) and extracellular regulated kinase (\n ERK<\/jats:styled-content>\n )1\/2 protein levels were analysed by Western blot.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Treatment with 10\u00a0mg\/kg Olme reduced ulceration, inflammatory cell infiltration,\n MPO<\/jats:styled-content>\n activity,\n MDA<\/jats:styled-content>\n levels,\n iNOS<\/jats:styled-content>\n and\n ERK<\/jats:styled-content>\n 1\/2 proteins levels,\n \n MIF<\/jats:styled-content>\n <\/jats:italic>\n expression and\n TNF<\/jats:styled-content>\n \u2010\u03b1 and\n IL<\/jats:styled-content>\n \u20101\u03b2 of levels and gene expression. These findings were associated with a significant increase in the immunostaining of\n IL<\/jats:styled-content>\n \u201010,\n FGF<\/jats:styled-content>\n \u20102 and\n TGF<\/jats:styled-content>\n \u2010\u03b2. In addition, gene expression of\n \n IL<\/jats:styled-content>\n \u20101\n <\/jats:italic>\n \u03b2\n , TNF\u2010<\/jats:italic>\n \u03b1\n , NF<\/jats:italic>\n \u2010\n \u03baBp65 MKP1<\/jats:italic>\n and\n ACE2<\/jats:italic>\n was decreased.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Olmesartan at a dose of 10\u00a0mg\/kg prevented the mucosal damage and inflammation associated with 5\u2010\n FU<\/jats:styled-content>\n \u2010induced\n OM<\/jats:styled-content>\n , increasing granulation and tissue repair.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jop.12775","type":"journal-article","created":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T06:13:09Z","timestamp":1534745589000},"page":"972-984","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Protective effect of angiotensin II receptor blocker against oxidative stress and inflammation in an oral mucositis experimental model"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9264-4695","authenticated-orcid":false,"given":"Aurigena Antunes de","family":"Ara\u00fajo","sequence":"first","affiliation":[{"name":"Postgraduate Programs in Public Health and Pharmaceutical Science Department of Biophysics and Pharmacology Federal University of Rio Grande Norte Natal Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena de Souza","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Public Health UFRN Natal Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Addison Carvalho Xavier de","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Pharmacology UFRN Natal Brazil"},{"name":"Postgraduate Program in Biological Science and Rede Nordeste de Biotecnologia\/Renorbio Federal University of Rio Grande Norte Natal 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Bernardo","family":"Guerra","sequence":"additional","affiliation":[{"name":"Postgraduate Programs in Postgraduate Program in Biological Science\/Pharmaceutical Science Department of Biophysical and Pharmacology UFRN Natal Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius Barreto","family":"Garcia","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Public Health UFRN Natal Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura de Souza","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Dentistry Federal University of Rio Grande Norte Natal Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimundo Fernandes de","family":"Ara\u00fajo Junior","sequence":"additional","affiliation":[{"name":"Postgraduate Programs in Functional & Structural Biology and Health Science Department of Morphology UFRN Natal 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