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Publications

Journal Article Epublish 2 citations

PubMed: 40632331 DOI: 10.1007/s11011-025-01668-w

Neuroprotective effects of Simvastatin against alcohol-induced oxidative stress and neurodegeneration in the Hippocampus of adolescent mice.

Metab Brain Dis 40(6):239

Authors: Robin du Preez, Tabo Mwila, Alice Efuntayo, Oladiran I Olateju

Affiliations

  • Department of Anatomical Sciences, School of Biomedical Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, Republic of South Africa.
  • Department of Anatomical Sciences, School of Biomedical Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, Republic of South Africa.

Abstract

Adolescent alcohol abuse in disadvantaged communities is a significant concern due to regulatory gaps. 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 mg/kg Simvastatin orally, followed by 20% alcohol (i.p.) or the controls (i.e., 5 mg/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 mg being more effective in females. MDA level and SOD activity remained unchanged. Simvastatin at 5 mg reduced alcohol's effect on PcNA-positive cells in both sexes, while 15 mg was more effective in females. For DCX-positive cells, 5 mg Simvastatin was protective in both sexes, but 15 mg showed no effect. Overall, Simvastatin exhibited antioxidant and neuroprotective effects against alcohol-induced hippocampal damage, suggesting its potential for treating alcohol-related brain disorders.

MeSH

Hippocampus, Simvastatin, Cells, Stress, Physiological, Brain, Oxidative Stress, Antioxidants, Adolescent