Vol. 9, Issue 11, Part A (2025)

Heavy metals like lead (Pb) are persistent pollutants causing oxidative stress, inflammation, and organ damage. Lead (Pb), a neurotoxicant and persistent pollutant from industrial and domestic sources, impairs cognitive and behavioral functions causing oxidative stress, inflammation and organ damage. This study evaluated the effect of Diospyros mespiliformis seed extract on lead toxicity induced changes in prefrontal cortex antioxidants and inflammatory cytokines level in mice. Twenty-five mice were divided into five groups (n = 5). Group A is control administered distilled water only, group B mice were induced with lead (50 mg/kg b.wt), group C mice received 200 mg/kg b.wt of D. mespiliformis while group D were given 400 mg/kg b. wt and group E were administered 100 mg/kg b.wt of vitamin E. Results indicated that Pb exposure (50 mg/kg, 28 days) induced neurotoxicity in the prefrontal cortex, increasing total protein, malondialdehyde (MDA), IL-6, TNF-α, and myeloperoxidase (MPO), while reducing protein thiols, catalase (CAT), and acetylcholinesterase (AChE) activity, reflecting oxidative stress, inflammation, and cholinergic disruption. Treatment with D. mespiliformis extract (200 and 400 mg/kg) or vitamin E (100 mg/kg) mitigated these effects. The 400 mg/kg extract dose-dependently reduced MDA, normalized TNF-α, IL-6, and CAT, often outperforming vitamin E, likely due to its antioxidant flavonoids and polyphenols. However, neither fully restored AChE or thiol levels, indicating limited efficacy against Pb’s direct binding. Vitamin E better reduced MPO. These findings highlighted D. mespiliformis’s potential as a neuroprotective agent against Pb-induced neurotoxicity, with efficacy rivaling vitamin E. Its low acute toxicity supports therapeutic promise, however, further studies on its active compounds, long-term safety, and optimization for thiol and cholinergic pathways are recommended.