Time- and Dose-Dependent Neurotoxicity of Aluminum Chloride: Oxidative Stress, Cholinergic Dysfunction, and Histopathological Alterations in Male Rat Brain
International Journal of Medical Toxicology and Forensic Medicine,
Vol. 16 (2026),
1 January 2026
https://doi.org/10.22037/ijmtfm.v16.53006
Abstract
Background: Aluminum (Al) is a ubiquitous environmental neurotoxin with a prolonged cerebral half-life. Chronic exposure has been implicated in oxidative damage, cholinergic impairment, and neurodegeneration; however, comprehensive time-course studies integrating biochemical and morphological endpoints remain limited. To evaluate the time- and dose-dependent effects of chronic aluminum chloride (AlCl₃) administration on brain oxidative stress markers, acetylcholinesterase (AChE) activity, and histopathological changes in male Wistar rats.
Methods: Ninety adult male rats were randomly divided into three groups (n = 30 each): control (distilled water), low-dose (100 mg/kg b.w. AlCl₃), and high-dose (200 mg/kg b.w. AlCl₃), administered orally for 30, 60, and 90 days. Brain aluminum residues were measured by graphite furnace atomic absorption spectrophotometry. Oxidative stress biomarkers (MDA, GSH, SOD, CAT) and serum AChE were quantified by ELISA. Brain sections were examined histopathologically with H&E staining.
Results: Brain aluminum accumulated in a time- and dose-dependent manner, peaking at 13.08±0.34 ppm at 90 days in the high-dose group versus 0.014±0.003 ppm in controls. Brain MDA rose from 0.34–0.38 in controls to a peak of 0.88±0.02, whereas SOD (64.80±2.60 to 38.86±1.37), CAT (91.6 to 62.40±3.63) and GSH (8.89 to 2.77±0.71) declined significantly (P≤ 0.01). Serum AChE fell from 482.10±0.62 to 112.90±1.21 ΔPh/20 min, a reduction of 76.6%. Histopathology revealed progressive cerebrovascular congestion, perivascular and perineuronal oedema, Virchow–Robin space dilatation, neurofibrillary tangles, and Purkinje cell chromatolysis with neuronophagia.
Conclusion: Chronic AlCl₃ exposure induces cumulative, irreversible neurotoxicity through synergistic oxidative and cholinergic mechanisms, underscoring the need for stricter environmental aluminum exposure limits and further investigation of neuroprotective interventions.
- Aluminum Chloride; Oxidative Stress; Neurotoxicity; Acetylcholinesterase; Brain; Rats, Wistar; Lipid Peroxidation; Histopathology.
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References
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