• Regulatory Role of Donepezil on Hippocampal Nitro-Oxidative Markers Following Bisphenol A Exposure
  • Shaghayegh Vahedi,1,* Delaram Eslimi Esfahani,2 Vahidesadat Abbasnia,3 Adel Salari,4
    1. Department of Animal Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
    2. KhU, University Sq., Shahid Beheshti Street, Karaj, Iran
    3. Department of Biology, Payame Noor University, Tehran, Iran
    4. Department of Animal Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran


  • Introduction: Bisphenol A (BPA), a widely used plastic-derived compound, disrupts cellular redox homeostasis by promoting excessive nitric oxide production, leading to nitrosative stress, mitochondrial dysfunction, and hippocampal neurodegeneration. Reduced activity of antioxidant enzymes, such as superoxide dismutase (SOD), along with elevated nitrite levels are key features of this imbalance. Donepezil, an acetylcholinesterase inhibitor with reported antioxidant properties, may exert neuroprotective effects by modulating these nitro-oxidative pathways. This study aimed to investigate the effects of donepezil on hippocampal nitrite levels and SOD activity in BPA-exposed rats.
  • Methods: Fifty-six male Wistar rats were randomly assigned to seven groups. Animals received oral treatments for four weeks: a BPA group (0.4 mg/kg/day), a donepezil-only group (10 mg/kg/day), and three BPA-treated groups co-administered donepezil at 1, 5, or 10 mg/kg/day. At the end of the experiment, hippocampal tissues were collected, and nitrite levels along with SOD activity were measured using standard biochemical assays. Data were analyzed by ANOVA, and statistical significance was set at p < 0.05.
  • Results: BPA exposure significantly increased hippocampal nitrite levels and decreased SOD activity compared to controls (p < 0.05). Donepezil treatment reversed these changes in a dose-dependent manner, reducing nitrite accumulation and enhancing SOD activity (p < 0.05).
  • Conclusion: The findings suggest that donepezil may restore hippocampal redox balance by regulating nitrosative pathways, highlighting its potential as a neuroprotective candidate against environmentally induced neurodegeneration.
  • Keywords: Bisphenol A; Donepezil; Hippocampus; Rats; Nitrosative Stress