ADAZE B. ENOGIERU

Cerebellar dysfunction (CD), via oxidative stress, is an established effect of lead (Pb), a known heavy metal, even at low exposure. Tetrapleura tetraptera (T. tetraptera) fruit exhibits various pharmacological properties, such as antioxidant and anti-inflammatory activities. This study investigated the activity of aqueous T. tetraptera fruit extract against lead acetate (PbA)-induced CD in Wistar rats. Sixty-eight Wistar rats were assigned to eight groups (n=8) and treated for twenty-eight days as follows: Groups A (control); B (100 mg/kg body weight (bw) of PbA; C (500 mg/kg bw of T. tetraptera and 100 mg/kg bw of PbA); D (1000 mg/kg bw of T. tetraptera and 100 mg/kg bw of PbA); E (200 mg/kg bw of Vitamin E and 100 mg/kg bw of PbA); F, G and H (500 mg/kg of T. tetraptera, 1000 mg/kg of T. tetraptera, and 200 mg/kg bw of Vitamin E), respectively. Subsequently, weights, neurobehavior, Pb concentration, antioxidant enzymes, lipid peroxidation, and cerebellar histology were assessed. High-performance liquid chromatography was used to identify phenolic compounds in T. tetraptera, and in-silico studies evaluated the binding interaction of some of the identified phenolic compounds (4-hydroxybenzoic acid and Resorcinol) to markers of apoptosis (caspase-3), inflammation (IL-6, TNF-α, and Nf-κB), and oxidative stress (NRF2). A significant decrease (p<0.05) in weights and antioxidant enzymes, as well as a significant increase (p<0.05) in neurobehavioral deficits, lipid peroxidation, Pb concentration, and alterations in cerebellar histoarchitecture were observed in the PbA-exposed rats when compared to control. However, co-treatment of PbA-exposed rats with T. tetraptera significantly attenuated (p<0.05) these PbA-induced effects. Additionally, in-silico studies revealed a high binding affinity of 4-hydroxybenzoic acid and Resorcinol to caspase-3, IL-6, TNF-α, Nf-κB, and NRF2, thus suggesting possible anti-apoptotic, anti-inflammatory, and antioxidant effects of T. tetraptera. This study provides research evidence suggesting that T. tetraptera has the potential for further development as a therapeutic agent against CD.

Cerebellar dysfunction, marked by impaired coordination and balance, often result from toxic or degenerative damage to cerebellar neurons. Excessive exposure to manganese chloride, a neurotoxic compound, disrupts neuronal integrity through oxidative stress and inflammation, leading to motor and structural deficits. Vanillin, a natural phenolic compound with strong antioxidant and anti-inflammatory properties, has shown potential in mitigating such neurotoxic effects. This study therefore investigated the protective effect of vanillin against manganese chloride–induced cerebellar toxicity in Wistar rats. Forty-eight (48) Wistar rats were randomly assigned into six groups (A-F). Group A rats served as the control group; Group B rats were administered 10 mg/kg body weight of manganese chloride; Group C rats were administered 20 mg/kg body weight of vanillin and 10 mg/kg body weight of manganese chloride; Group D was administered 40 mg/kg body weight of manganese chloride and 40 mg/kg body weight of vanillin; Group E was administered 20 mg/kg body weight of vanillin; Group F was given 40 mg/kg body weight of vanillin. All administrations lasted for twentyeight (28) days. Neurobehavioural activities were evaluated using the open field, movement initiation, step and string Tests. Results from the study revealed that rats exposed to manganese chloride exhibited significant (p<0.05) weight loss, motor deficit, impaired antioxidant defense, elevated lipid peroxidation and degeneration of Purkinje cells and molecular layer neurons. However, pre-treatment with Vanillin significantly (p<0.05) mitigated these manganese chloride-induced cerebellar alterations in Wistar rats. Overall, the findings from this study indicate that vanillin possesses strong antioxidant properties, supporting its potential as an effective therapeutic agent for the treatment and management of manganese chlorideinduced cerebellar dysfunction

Hippocampal dysfunction, often linked to learning and memory impairments, can result from neurodegeneration or exposure to toxic agents. Manganese chloride, a neurotoxic compound, accumulates in the hippocampus and disrupts neuronal signalling through oxidative stress, mitochondrial dysfunction, and inflammation, leading to cognitive deficits. Vanillin, a natural phenolic compound with antioxidant and anti-inflammatory properties, has shown potential in protecting against such neurotoxic damage and preserving hippocampal integrity. Accordingly, the aim of this study was to evaluate the activity of vanillin on manganese chloride-induced hippocampal toxicity in Wistar rats. Forty-eight (48) adult Wistar rats were randomly assigned into six groups (A-F). Group A served as control; Group B received 10 mg/kg body weight [BW] of manganese chloride only; Group C received 20 mg/kg BW of vanillin and 10 mg/kg BW of manganese chloride. Group D received 40 mg/kg BW of vanillin and 10 mg/kg BW of manganese chloride. Group E received 20 mg/kg BW of vanillin only and Group F received 40 mg/kg BW of vanillin only. All administrations, lasted for twenty-eight (28) days. Nneurobehavioral activities were evaluated using the Novel object recognition and elevated plus maze tests.

Hippocampal dysfunction is a key feature of several neurocognitive disorders and may arise from factors such as congenital defects, neurodegeneration, or exposure to neurotoxicants. Lead (Pb), a potent heavy metal, crosses the blood-brain barrier and accumulates in the hippocampus, where it disrupts calcium signaling and induces oxidative stress, thus contributing to neuronal damage and cognitive deficits. Evidence suggests that dietary antioxidants may help mitigate Pb-induced oxidative damage and preserve hippocampal function. Accordingly, this study investigated the protective activity of aqueous Rosmarinus officinalis leaf extract (R. officinalis) against lead acetate (PbA) induced hippocampal toxicity. Forty-eight (48) adult Wistar rats were randomly assigned into six groups (A-F). Group A served as control; Group B received 100 mg/kg body weight [bw] of PbA only; Group C received 100 mg/kg bw of R. officinalis extract and PbA; Group D received 200 mg/kg bw of R. officinalis extract and PbA; Group E received 100 mg/kg bw of R. officinalis extract only and Group F received 200 mg/kg bw of R. officinalis extract only. All administrations, via an orogastric tube, lasted for twenty-eight (28) days. Thereafter, neurobehavioral activities were evaluated using the Novel object recognition, Y-maze and Elevated plus maze tests. Following the sacrifice of the experimental rats, the hippocampi were collected for Pb concentration, antioxidant enzymes activity, lipid peroxidation, acetylcholinesterase activity, nitric oxide levels, and histological assessments as well as apoptosis. The findings showed that PbAexposed rats exhibited significant (p<0.05) weight loss, cognitive and memory impairments, dysregulated antioxidant enzymes activity, and increased lipid peroxidation, nitric oxide, Pb and AChE levels, along with atrophy and vacuolation of pyramidal cells and astrocytes in the CA1 region of the hippocampus. Also, there was an upregulation of Caspase-3 expression in the hippocampus of experimental rats exposed to PbA, indicating apoptosis as a possible mechanism of action. However, pretreatment with R. officinalis significantly (p<0.05) mitigated the adverse effects induced by PbA in the hippocampus of experimental rats suggesting strong metal-chelating, anti-cholinesterase, and NO-scavenging effects. Similarly, the downregulation of caspase-3 expression in the hippocampus of PbA-exposed rats following pretreatment with R. officinalis supports its anti-apoptotic potential. Overall, these findings suggest that R. officinalis exhibits potent antioxidant, metal-chelating, nitric oxide-scavenging, anti-cholinesterase and anti-apoptotic properties, thus providing novel evidence supporting R. officinalis as a promising neuroprotective agent with potential for drug development against hippocampal dysfunction.

Vitamin E, a fat-soluble antioxidant, plays a crucial role in protecting cellular membranes from oxidative damage. Its neuroprotective properties have garnered attention in recent studies, particularly concerning neurotoxicity induced by aluminum chloride (AlCl3). Exposure to AlCl3 has been linked to cognitive deficits and neurodegenerative changes in the brain, making it a significant concern in neurobiology. Research has demonstrated that Vitamin E administration can mitigate the adverse effects of AlCl3 by reducing oxidative stress and inflammation in the brain. This research aims to explore the activity of Vitamin E in the cerebellum of Wistar rats treated with aluminum chloride. A total of twenty-eight (28) adult Wistar rats with an average weight of 180g were used for this study. They were randomly assigned into four groups (A, B, C, and D) with each group consisting of Seven rats. Group A served as control, Group B was administered 5mg/kg of Aluminum chloride, Group C was
administered 5mg/kg of Aluminum chloride + Vitamin E and Group E was administered Vitamin E only. Administration lasted for 28 days and was done via oral route. Neurobehavioural activity was assessed after administration on the 28th day. The rats
were ;sacrificed after the neurobehavioural activity was assessed. The key findings of this study suggest that Vitamin E administration mitigated the adverse effects of aluminum chloride exposure on the cerebellum of Wistar rats by reducing oxidative stress, improving antioxidant enzyme activity, and preventing neurodegeneration in the Purkinje cell layer. The findings of
this study indicate that Vitamin E can effectively protect the cerebellum of Wistar rats against the neurotoxic effects of aluminum chloride exposure by modulating oxidative stress and improving antioxidant defense mechanismsUN