DANIEL ODIANOSEN ESEINE

Cerebral dysfunction, a hallmark of various neurocognitive disorders, may result from congenital anomalies, progressive neurodegeneration, or exposure to neurotoxic agents. Lead (Pb), a highly toxic heavy metal, readily crosses the blood–brain barrier and accumulates in the cerebrum, where it disrupts calcium homeostasis and promotes oxidative stress. This cascade contributes to neuronal injury and cognitive decline. Emerging evidence suggests that dietary antioxidants can counteract lead-induced oxidative damage and help preserve cerebral integrity. This study evaluated the neuroprotective effects of aqueous Tetrapleura tetraptera (TT) fruit extract on lead acetate induced cerebral toxicity. Sixty-four adult Wistar rats were randomly divided into eight treatment groups (n=8) and treated for 28 days as follows: Group A (control – 1 mL distilled water), Group B (Pb only, 100 mg/kg [bw]), Group C (TT - 500 mg/kg [bw] + Pb - 100mg/kg [bw]), Group D (TT - 1000 mg/kg [bw] + Pb – 100 mg/kg [bw]), Group E (Vitamin E – 200 mg/kg [bw] + Pb - 100mg/kg [bw]), Group F (TT only - 500 mg/kg [bw]), Group G (TT only - 1000 mg/kg [bw]), and Group H (Vitamin E only – 200 mg/kg [bw]). High Performance Liquid Chromatography (HPLC) was carried out to identify the phytochemicals contained in the extract. Molecular docking results showed the polyphenols, catechol and phloroglucinol, displayed a higher binding affinity with Caspase 3, IL-6 and comparable binding affinity with NRF2 against standard drugs like Levodopa and Clonazepam. Pre-sacrifice, neurobehavioral assessments were conducted to evaluate cerebral dysfunction. Lead only exposed rats showed significant decrease in rearing frequency, and increase in grooming, thigmotaxis, sniffing, immobility time respectively. Post-sacrifice, cerebral tissues were analysed for lead concentration, antioxidant enzymes activity, lipid peroxidation and histopathological changes. Lead only exposed rats showed significant impaired (p<0.05) weight gain and antioxidant enzymes function, elevated lipid peroxidation, and increased cerebral lead levels. Histological analysis revealed vacuolation of granular cells and presence of pyknotic nuclei in the prefrontal cortex. However, pretreatment with Tetrapleura tetraptera significantly (p<0.05) mitigated these effects in lead-exposed rats suggesting strong neuroprotective properties. The study identifies Tetrapleura tetraptera potential as a natural, neuroprotective and therapeutic agent against lead-induced cerebral dysfunction. Further studies exploring the application of Tetrapleura tetraptera in other models of cerebral dysfunction are recommended.