Quercetin Mitigates Aluminium Chloride-induced Neurotoxicity by Modulating Oxidative Stress, Neuroinflammation, and Neurotransmitter Dysregulation in Rats

 Fatoki Tunji Micheal¹, Ajibola Toheeb Adesumbo², Onaolapo Olakunle James³, Onaolapo Adejoke Yetunde^{1, 4} 

1. Department of Anatomy, Faculty of Basic Medical Science, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria. 

2. Department of Anatomy, Faculty of Basic Medical Sciences, Federal University Oye-Ekiti, Ekiti State, Nigeria  

3. Behavioural Neuroscience and Neuropharmacology Unit, Department of Pharmacology and Therapeutics, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria  

4. Behavioural Neuroscience and Neurobiology Unit, Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria 

ABSTRACT

Memory impairment, characterized by reduced ability to recall facts, information, and experiences, is increasingly recognized as a major public health concern. This trend is largely driven by the rising prevalence of age-related cognitive decline and Alzheimer’s disease within the aging population. Aluminium chloride (AlCl₃), a well-established neurotoxicant, induces neurobehavioral and biochemical alterations that mimickey features of neurodegenerative disorders, thus serving as a reliable experimental model for evaluating neuroprotective agents. This study assessed the neuroprotective efficacy of quercetin in a rat model of AlCl₃-induced neurotoxicity. Fifty adult male rats (n = 10 per group) were randomly assigned into five groups. Neurotoxicity was induced by oral administration of AlCl₃ (100 mg/kg/day) for 14 days. Subsequently, from days 14 to 35, rats received daily treatments of quercetin (100 or 200 mg/kg), donepezil (3 mg/kg), or vehicle control. AlCl₃ exposure significantly impaired body weight gain, feed intake, locomotor activity, grooming behaviour, and spatial memory performance. Quercetin treatment markedly ameliorated these deficits, as evidenced by improved performance in Y-maze and radial-arm maze tasks. Biochemical analysis revealed that quercetin significantly reduced lipid peroxidation, enhanced total antioxidant capacity, and modulated inflammatory responses by decreasing pro-inflammatory cytokines (IL-1β, TNF-α) and elevating anti-inflammatory IL-10 levels. Furthermore, quercetin restored acetylcholine and brain-derived neurotrophic factor (BDNF) concentrations and preserved hippocampal cytoarchitecture, as demonstrated by histopathological assessment. These findings highlight quercetin’s therapeutic potential in mitigating aluminium-induced neurotoxicity and suggest its utility in the management of neurodegenerative disorders. 

KEYWORDS: Aluminium Chloride; Donepezil; Neurotoxicity; Neuroinflammation; Neuroprotection; Oxidative stress