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It disrupts brain development, particularly affecting the hippocampus, which is vulnerable to alcohol-induced oxidative stress, resulting in impaired neuronal signalling, increased cell death, and reduced neurogenesis. Simvastatin, a cholesterol-lowering drug, has neuroprotective and antioxidant effects, but its potential in protecting against alcohol-related brain damage is unclear. This study examined the protective effects of Simvastatin in four-week-old C57BL\/6J mice administered 20% alcohol (intraperitoneal, i.p.), 5 or 15\u00a0mg\/kg Simvastatin orally, followed by 20% alcohol (i.p.) or the controls (i.e., 5\u00a0mg\/kg Simvastatin only or no treatment). After 28 days, the harvested brains underwent biochemical or immunohistochemical (IHC) analysis. Biochemical analyses measured malondialdehyde (MDA) levels, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity in homogenised hippocampal samples and IHC involved immunolabelling for PcNA or DCX. PcNA- or DCX-positive cells in the suprapyramidal blade of the dentate gyrus were counted using QuPath software. Alcohol elevated GSH-Px activity, indicating oxidative damage, but both Simvastatin concentrations reduced this, with 15\u00a0mg being more effective in females. MDA level and SOD activity remained unchanged. Simvastatin at 5\u00a0mg reduced alcohol\u2019s effect on PcNA-positive cells in both sexes, while 15\u00a0mg was more effective in females. For DCX-positive cells, 5\u00a0mg Simvastatin was protective in both sexes, but 15\u00a0mg showed no effect. Overall, Simvastatin exhibited antioxidant and neuroprotective effects against alcohol-induced hippocampal damage, suggesting its potential for treating alcohol-related brain disorders.<\/jats:p>","DOI":"10.1007\/s11011-025-01668-w","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:26:30Z","timestamp":1752139590000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuroprotective effects of Simvastatin against alcohol-induced oxidative stress and neurodegeneration in the Hippocampus of adolescent mice"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7234-0424","authenticated-orcid":false,"given":"Robin du","family":"Preez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5502-9626","authenticated-orcid":false,"given":"Tabo","family":"Mwila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4412-2507","authenticated-orcid":false,"given":"Alice","family":"Efuntayo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4415-1877","authenticated-orcid":false,"given":"Oladiran I.","family":"Olateju","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"issue":"4","key":"1668_CR1","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1017\/S1461145705005286","volume":"8","author":"E \u00c5berg","year":"2005","unstructured":"\u00c5berg E et al (2005) Moderate ethanol consumption increases hippocampal cell proliferation and neurogenesis in the adult mouse. 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