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We examined the preventive effects of acetylated oligopeptides (AOP) from whey protein on iron\u2010induced hippocampal damage compared to <jats:italic>N<\/jats:italic>\u2010acetyl cysteine (NAC). This 5\u2010week study used 40 male albino rats. At the start, all rats received 150\u2009mg\/kg\/day of oral NAC for a week. The 40 animals were then randomly divided into four groups: Group I (control) received a normal diet; Group II (iron overload) received 60\u2009mg\/kg\/day intraperitoneal iron dextran 5 days a week for 4 weeks; Group III (NAC group) received 150\u2009mg\/kg\/day NAC and iron dextran; and Group IV (AOP group) received 150\u2009mg\/kg\/day AOP and iron dextran. Enzyme\u2010linked immunosorbent assay, spectrophotometry, and qRT\u2010PCR were used to measure MMP\u20109, tissue inhibitor metalloproteinase\u20101 (TIMP\u20101), MDA, reduced glutathione (GSH) levels, and nuclear factor erythroid 2\u2010related factor 2 (Nrf2) and heme oxygenase\u20101 (HO\u20101) gene expression. Histopathological and immunohistochemical detection of nestin, claudin, caspase, and GFAP was also done. MMP\u20109, TIMP\u20101, MDA, caspase, and GFAP rose in the iron overload group, while GSH, Nrf2, HO\u20101, nestin, and claudin decreased. The NAC and AOP administrations improved iron overload\u2010induced biochemical and histological alterations. We found that AOP and NAC can protect the brain hippocampus from iron overload, improve BBB disruption, and provide neuroprotection with mostly no significant difference from healthy controls.<\/jats:p>","DOI":"10.1002\/cbf.3958","type":"journal-article","created":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T00:29:40Z","timestamp":1708734580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Acetylated oligopeptide and <i>N<\/i>\u2010acetylcysteine protect against iron overload\u2010induced dentate gyrus hippocampal degeneration through upregulation of Nestin and Nrf2\/HO\u20101 and downregulation of MMP\u20109\/TIMP\u20101 and GFAP"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7567-7022","authenticated-orcid":false,"given":"Amira A.","family":"Kamel","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine Assiut University  Assiut Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed Y.","family":"Nassar","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine Assiut University  Assiut Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma Y.","family":"Meligy","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry and Basic Medical Sciences, Faculty of Dentistry University of Petra  Amman Jordan"},{"name":"Department of Histology and Cell Biology, Faculty of Medicine Assiut University  Assiut Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yomna A.","family":"Omar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Assiut University  Assiut Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gamal A. 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