{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:09:13Z","timestamp":1788901753659,"version":"build-2803163510"},"reference-count":38,"publisher":"S. Karger AG","issue":"5-6","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[2021]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;\/i&gt;&lt;\/b&gt; Periodontitis is a lifestyle-related disease that is characterized by chronic inflammation in gingival tissue. Febuxostat, a xanthine oxidase inhibitor, exerts anti-inflammatory and antioxidant effects. &lt;b&gt;&lt;i&gt;Objective:&lt;\/i&gt;&lt;\/b&gt; The present study investigated the effects of febuxostat on periodontitis in a rat model. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; Male Wistar rats were divided into 3 groups: control, periodontitis, and febuxostat-treated periodontitis groups. Periodontitis was induced by placing a ligature wire around the 2nd maxillary molar and the administration of febuxostat (5 mg\/kg\/day) was then initiated. After 4 weeks, alveolar bone loss was assessed by micro-computed tomography and methylene blue staining. The expression of osteoprotegerin (OPG), a bone resorption inhibitor, was detected by quantitative RT-PCR and immunological staining, and the number of osteoclasts in gingival tissue was assessed by tartrate-resistant acid phosphatase staining. The mRNA and protein expression levels of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-\u03b1), and interleukin-1 beta (IL-1\u03b2), in gingival tissue were measured using quantitative RT-PCR and immunological staining. Oxidative stress in gingival tissue was evaluated by the expression of 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2-deoxyguanosine (8-OHdG). To clarify the systemic effects of periodontitis, blood pressure and glucose tolerance were examined. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; In rats with periodontitis, alveolar bone resorption was associated with reductions in OPG and increases in osteoclast numbers. The gingival expression of TNF-\u03b1, IL-1\u03b2, 4-HNE, and 8-OHdG was up-regulated in rats with periodontitis. Febuxostat significantly reduced alveolar bone loss, proinflammatory cytokine levels, and oxidative stress. It also attenuated periodontitis-induced glucose intolerance and blood pressure elevations. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; Febuxostat prevented the progression of periodontitis and associated systemic effects by inhibiting proinflammatory mediators and oxidative stress. <\/jats:p>","DOI":"10.1159\/000513034","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T07:53:32Z","timestamp":1616486012000},"page":"294-304","source":"Crossref","is-referenced-by-count":18,"title":["Febuxostat Attenuates the Progression of Periodontitis in Rats"],"prefix":"10.1159","volume":"106","author":[{"given":"Naseratun","family":"Nessa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Kobara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroe","family":"Toba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiro","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narisato","family":"Kanamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pezzotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Nakata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12222"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2007.01091.x"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2013.130066"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.07.034"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-010-0458-y"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.7243\/2053-5775-2-4"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2008.070605"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.10.031"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343669"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.234559"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.09.032"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-015-1202-6"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.105884"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1038\/srep04554"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00454.2007"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22784"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00988"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2013.05.002"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13096"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2007.060252"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134784"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12600"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2018.6972"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311401"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpu225"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00101.2016"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-007-0047-1"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-007-0636-3"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00338"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2006.00946.x"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.3390\/md14040070"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2016.03.004"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-016-3612-2"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194680"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2018-0731"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1710895"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz119"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.033992"}],"container-title":["Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/513034","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/513034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:10:06Z","timestamp":1745424606000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000513034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021]]},"references-count":38,"journal-issue":{"issue":"5-6","published-online":{"date-parts":[[2021,5,26]]},"published-print":{"date-parts":[[2021,5,25]]}},"URL":"https:\/\/doi.org\/10.1159\/000513034","archive":["Portico"],"relation":{},"ISSN":["0031-7012","1423-0313"],"issn-type":[{"value":"0031-7012","type":"print"},{"value":"1423-0313","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021]]}}}