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Gallic acid (GA), a natural phenolic compound with potent antioxidant and anti-inflammatory properties, has been proposed as a protective agent against drug-induced tissue injury. This study investigated the prophylactic and therapeutic effects of GA on zoledronic acid (ZOA)\u2013induced MRONJ in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Thirty-two adult female Wistar albino rats were randomly divided into four groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098): Control, MRONJ (ZOA\u2009+\u2009tooth extraction), MRONJ\u2009+\u2009Pre-GA (prophylactic GA), and MRONJ\u2009+\u2009Post-GA (therapeutic GA). MRONJ was induced by intraperitoneal ZOA (0.06\u00a0mg\/kg\/week, 5 weeks) followed by mandibular molar extraction. GA (100\u00a0mg\/kg, i.p.) was administered either before or after ZOA exposure for 7 days. Mandibular tissues were analyzed histopathologically, immunohistochemically (Fibroblast growth factor [FGF], transforming growth factor beta 1 [TGF-1\u03b2], tumor necrosis factor alpha [TNF-\u03b1]), and molecularly (TNF-\u03b1, TGF-1\u03b2, endothelial nitric oxide synthase [eNOS], cytochrome c [Cyt-C], caspase-3 [Cas-3], protein kinase RNA-like ER kinase [PERK], C\/EBP homologous protein [CHOP]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MRONJ rats exhibited severe osteonecrosis, increased inflammation and fibrosis, disrupted collagen organization, elevated osteoclast activity, and suppressed osteoblast function. Immunohistochemistry revealed significant downregulation of FGF and TGF-1\u03b2 with a concomitant rise in TNF-\u03b1. Gene expression analyses showed upregulation of TNF-\u03b1, TGF-1\u03b2, CHOP, PERK, Cyt-C, and Cas-3, along with downregulation of eNOS. GA administration markedly ameliorated these alterations, restoring bone architecture, normalizing growth factor expression, suppressing pro-inflammatory and apoptotic signaling, and reducing ER stress. The prophylactic regimen showed the most pronounced protective efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GA confers both preventive and therapeutic benefits against MRONJ by mitigating oxidative stress, inflammation, fibrosis, ER stress and mitochondrial apoptosis. These findings suggest that GA may represent a promising adjuvant strategy for managing or preventing MRONJ in patients receiving long-term antiresorptive therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12903-026-07732-w","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T02:35:54Z","timestamp":1769222154000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective and therapeutic effects of gallic acid on medication-related osteonecrosis of the jaw in rats: modulation of inflammation, fibrosis and endoplasmic reticulum\/mitochondrial stress pathways"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2303-1884","authenticated-orcid":false,"given":"Tayfun","family":"Yaz\u0131c\u0131","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3326-0047","authenticated-orcid":false,"given":"Mustafa","family":"Isleyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2284-7161","authenticated-orcid":false,"given":"Aybike","family":"Imeci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-035X","authenticated-orcid":false,"given":"Halil","family":"Asci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1087-4874","authenticated-orcid":false,"given":"Muhammet Yusuf","family":"Tepebasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1743-412X","authenticated-orcid":false,"given":"Abdurrahman","family":"G\u00fclal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3768-7996","authenticated-orcid":false,"given":"Oznur","family":"Kolay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serife","family":"Tasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6878-2243","authenticated-orcid":false,"given":"Sefa Erdem","family":"Karap\u0131nar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1835-1082","authenticated-orcid":false,"given":"Ozlem","family":"Ozmen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,24]]},"reference":[{"key":"7732_CR1","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.sdentj.2022.01.003","volume":"34","author":"R AlRowis","year":"2022","unstructured":"AlRowis R, Aldawood A, AlOtaibi M, Alnasser E, AlSaif I, Aljaber A, et al. 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Front Pharmacol. 2025;16:1549526. https:\/\/doi.org\/10.3389\/fphar.2025.1549526.","journal-title":"Front Pharmacol"}],"container-title":["BMC Oral Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12903-026-07732-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-026-07732-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-026-07732-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:03:41Z","timestamp":1781629421000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12903-026-07732-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,24]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["7732"],"URL":"https:\/\/doi.org\/10.1186\/s12903-026-07732-w","relation":{},"ISSN":["1472-6831"],"issn-type":[{"value":"1472-6831","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,24]]},"assertion":[{"value":"12 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal experiments were approved by the Suleyman Demirel University Local Animal Ethics Committee with the decision dated 10\/04\/2025 no: 04\/490. All procedures were performed in accordance with the ARRIVE 2.0 guidelines and internationally accepted standards for animal experimentation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"211"}}