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This study evaluates the protective effects of gallic acid (GA), a natural polyphenol with potent antioxidant and anti-inflammatory properties, against ACR-induced lung injury. Fifty male rats were divided into five groups: Control, ACR, GA50\u2009+\u2009ACR, GA100\u2009+\u2009ACR, and GA100. Lung tissues were analyzed biochemically, histopathologically, immunohistochemically, and via immunofluorescence. GA exhibited dose-dependent protective effects by enhancing antioxidant defenses through Nrf-2 (43% increase) and HO-1 activation and reducing lipid peroxidation markers (MDA decreased by 38%). GA also suppressed pro-inflammatory mediators (TNF-\u03b1 reduced by 35%) and restored anti-inflammatory levels by modulating the NF-\u03baB pathway. Furthermore, GA reduced apoptosis (Caspase-3 activity decreased by 30%) and preserved lung tissue integrity by mitigating oxidative DNA damage (8-OHdG levels reduced by 29%) and pro-apoptotic signaling (Bax levels reduced by 34%). Computational analyses demonstrated GA's interaction with the KEAP1 protein, supporting its role in activating the KEAP1-Nrf2 pathway. These findings highlight GA's antioxidant, anti-inflammatory, and anti-apoptotic properties, suggesting its therapeutic potential for protecting against ACR-induced lung injury and paving the way for future research in lung health and toxicology.<\/jats:p>","DOI":"10.1007\/s00210-025-03996-1","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:52:10Z","timestamp":1741765930000},"page":"11821-11837","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Gallic acid\u2019s protective mechanisms against acrylamide-induced pulmonary injury: in vivo and in silico insights into the Nrf-2\/HO-1\/NF\u03baB pathway modulation"],"prefix":"10.1007","volume":"398","author":[{"given":"Merve","family":"Bolat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samet","family":"Tekin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130smail","family":"Bolat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asl\u0131han","family":"Atasever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burak","family":"\u00c7inar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"Da\u011f","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emin","family":"\u015eeng\u00fcl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serkan","family":"Yildirim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Warda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fikret","family":"\u00c7elebi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"3996_CR1","doi-asserted-by":"publisher","first-page":"37709","DOI":"10.1007\/s11356-020-09516-3","volume":"27","author":"MM Abdel-Daim","year":"2020","unstructured":"Abdel-Daim MM, Abo El-Ela FI, Alshahrani FK, Bin-Jumah M, Al-Zharani M, Almutairi B, Alkahtani S (2020) Protective effects of thymoquinone against acrylamide-induced liver, kidney and brain oxidative damage in rats. 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