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

Onaolapo, A. Y.; Onaolapo, O.; Ajibola, T.; Fatoki, T.

doi:10.1101/2025.09.11.675655

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bioRxiv · 10.1101/2025.09.11.675655

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

Onaolapo, A. Y.·Onaolapo, O.·Ajibola, T.·Fatoki, T.

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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 Alzheimers disease within the aging population. Aluminium chloride (AlCl{square}), a well-established neurotoxicant, induces neurobehavioral and biochemical alterations that mimic key 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 AlCl{square}-induced neurotoxicity. Fifty adult male rats (n = 10 per group) were randomly assigned into five groups. Neurotoxicity was induced by oral administration of AlCl{square} (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. AlCl{square} 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-1{beta}, TNF-) 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 quercetins therapeutic potential in mitigating aluminium-induced neurotoxicity and suggest its utility in the management of neurodegenerative disorders.

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Onaolapo, A. Y., Onaolapo, O., Ajibola, T., Fatoki, T.. 2025-09-11. Quercetin Mitigates Aluminium Chloride-Induced Neurotoxicity by Modulating Oxidative Stress, Neuroinflammation, and Neurotransmitter Dysregulation in Rats. https://doi.org/10.1101/2025.09.11.675655

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