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The current study was conducted to survey the antioxidant effect of grape seeds extract nanoparticles (GS extract NPs) against CCl<jats:sub>4<\/jats:sub>-induced oxidative stress, hepatic dysfunction and inflammatory changes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Hydroethanolic Grape seed (GS) extract was prepared and characterized using high performance liquid chromatography (HPLC), inductively coupled plasma\u2013mass spectrometry (ICP-MS) and gas chromatography\u2013mass spectrometry (GC-MS). Then, GS extract NPs were synthesized and in vitro antioxidant, anticoagulant, cytotoxicity and anti-inflammatory testes confirmed biological activity. Finally, Twenty-five male Sprague-Dawley rats were divided into five groups (<jats:italic>n<\/jats:italic>\u2009=\u20095\/group). Either GS extract (200\u00a0mg\/kg\/day) or GS extract NPs (100\u00a0mg\/kg\/day) were orally administrated independently to CCL<jats:sub>4<\/jats:sub>-intoxicated (0.5\u00a0ml\/kg twice a week for 3 weeks) rats. Four weeks after the treatment, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) were monitored. In addition, hepatic Malondialdehyde (MDA), Superoxide dismutases (SOD), Glutathione (GSH) and catalase (CAT) and hepatic inflammatory cytokines were assessed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>GS extract NPs were spherical-shaped and regular particles (size: 16.5 to 22.5\u00a0nm and zeta potential: -39.42 mv). CCL<jats:sub>4<\/jats:sub> -intoxicated rats showed increase of serum ALT, AST, ALP, elevation in MDA level accompanied by a decline in SOD, GSH and CAT levels in liver, compared with CCL<jats:sub>4<\/jats:sub>-untreated rats. Immunologically, serum C-Reactive Protein (CRP) and hepatic interleukin 1\u03b2 (IL-1\u03b2), IL-4, IL-6 and Tumor Necrosis Factor-alpha (TNF-\u03b1) showed significant elevation, compared with CCL<jats:sub>4<\/jats:sub> -untreated rats. Conversely, GS extract NPs supplementation potentially ameliorate hepatic functions by normalization of serum ALT, AST and ALP, reduced MDA level, improved antioxidant CAT, regulated liver inflammatory cytokines via maximal reduction of hepatic IL-1\u03b2, IL-4, IL-6 and TNF-\u03b1. <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>GS extract NPs augmented the antioxidant and anti-inflammatory properties of GS extract thereby protecting the liver against oxidative stress induced by CCl<jats:sub>4<\/jats:sub> as hepatic xenobiotic.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical trial number<\/jats:title>\n            <jats:p>Not applicable.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12906-025-05005-7","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T06:54:08Z","timestamp":1752908048000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nanoparticles from grape seed extract inhibit inflammatory cytokines and ameliorate CCl4-induced hepatotoxicity"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2101-3076","authenticated-orcid":false,"given":"Neveen Adel","family":"Madbouly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa Mohammad","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyaa Ahmed","family":"Farid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,19]]},"reference":[{"key":"5005_CR1","doi-asserted-by":"publisher","first-page":"129193","DOI":"10.1016\/j.jhazmat.2022.129193","volume":"436","author":"X Jia","year":"2022","unstructured":"Jia X, Wen X, Russo DP, Aleksunes LM, Zhu H. 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