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Eugenol (EU), a natural phenolic compound known for its antioxidant and anti-inflammatory properties, was evaluated for its neuroprotective efficacy in ACR-induced brain toxicity in rats. Male Wistar rats were orally administered ACR (20\u00a0mg\/kg\/day) for four weeks to induce neurotoxicity, with concurrent administration of EU at two doses (50 and 100\u00a0mg\/kg\/day). Behavioral assessments, including foot splay, gait score, and rotarod performance, were conducted to evaluate motor coordination and neuromuscular integrity. Biochemical analyses revealed that ACR significantly elevated markers of oxidative and nitrosative stress, suppressed antioxidant defense mechanisms. Furthermore, ACR induced significant upregulation of pro-inflammatory mediators (NLRP3, p-NF-\u03baB, IL-1\u03b2), as well as apoptosis markers such as caspase-3, alongside prominent histopathological alterations and astrocyte activation (evidenced by increased GFAP expression). Treatment with EU resulted in a dose-dependent amelioration of these neurotoxic effects. Notably, EU restored motor function, attenuated oxidative\/nitrosative damage, and reactivated the Nrf2\/NQO1\/HO-1 antioxidant pathway. Simultaneously, it significantly downregulated the expression of NLRP3, p-NF-\u03baB, and IL-1\u03b2, indicating strong anti-inflammatory action. Histological analysis confirmed preservation of neuronal architecture, while immunohistochemistry showed reduced caspase-3 and GFAP expression in EU-treated groups. These findings suggest that EU exerts potent neuroprotective effects against ACR-induced brain toxicity, primarily through modulation of redox balance, suppression of neuroinflammation, and inhibition of apoptotic cell death, via targeting both the Nrf2-mediated antioxidant system and the NLRP3\/NF-\u03baB\/IL-1\u03b2 inflammatory cascade.<\/jats:p>","DOI":"10.1038\/s41598-025-34650-8","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:06:15Z","timestamp":1769155575000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neuroprotective potential of eugenol against acrylamide-induced brain toxicity by regulating Nrf2\/NQO1\/HO-1 and NLRP3\/NF-\u03baB\/IL-1\u03b2 signaling cascades"],"prefix":"10.1038","volume":"16","author":[{"given":"Sara M.","family":"Baraka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosra A.","family":"Hussien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar A.","family":"Ahmed-Farid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5401-5422","authenticated-orcid":false,"given":"Dalia O.","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"34650_CR1","doi-asserted-by":"publisher","unstructured":"Tepe, Y. & Cebi, A. 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