Adaze B. Enogieru

ACTIVITY OF CATECHIN IN THE CEREBELLUM OF MERCURY CHLORIDE-TREATED WISTAR RATS

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Abstract
Reports indicate that cerebellar disorders are induced by exposure to heavy metals, such as Mercury, via oxidative stress, neuroinflammation, and Purkinje cell apoptosis, thus disrupting motor coordination and cognitive processing. Catechin (CA), a flavonoid in green tea, exhibits antioxidant, anti-tumor, and anti-inflammatory effects, making it a potential therapeutic agent against heavy metal toxicity. This study investigated the activity of catechin in the cerebellum of Wistar rats exposed to Mercury chloride. Sixty-four Wistar rats were randomly assigned into eight groups (n=8), and treated for twenty-eight days, as follows; A (control), B (5 mg/kg body weight [bw] of mercury chloride [HgCl2]), C (10 mg/kg bw of CA and HgCl2), D (20 mg/kg bw of CA and HgCl2), E (200 mg/kg bw of Vitamin E and HgCl2), F (10 mg/kg bw of Catechin only), G (20 mg/kg bw of Catechin only) and H (200 mg/kg bw of Vitamin E only). Thereafter, weights, neurobehavioral activities, mercury concentration, antioxidant enzymes activity, lipid peroxidation, and histology of the cerebellum were assessed. In-silico studies were utilized to investigate multi-targeted protective potential of catechin, by assessing its interactions with key mediators of inflammation, oxidative stress, and apoptosis. Findings showed that HgCl₂ treatment significantly decreased (p<0.05) body weight and antioxidant enzymes, while significantly increasing (p<0.05) lipid peroxidation, mercury concentration, and neurobehavioral deficits, with cerebellar histology revealing Purkinje cell alterations, vacuolations, and pyknotic nuclei. Conversely, groups pre-treated with CA showed an attenuation of the HgCl2-induced adverse effects. In-silico results showed catechin bound more strongly to Nrf2, TNF-α, IL-6, NF-ĸB, and Caspase-3 than amantadine and riluzole, highlighting its multi-targeted antioxidant, anti-inflammatory, and anti-apoptotic potential.
This study highlights catechin as a safe, natural therapeutic for HgCl2-induced cerebellar disorder, offering a promising alternative to conventional drugs with fewer side effects Furtherstudies exploring the translational application of catechin in clinical trials are recommended
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co-supervisor

ACTIVITY OF AQUEOUS Tetrapleura tetraptera FRUIT EXTRACT ON THE CEREBRUM OF LEAD ACETATEEXPOSED RATS

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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.
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co-supervisor

EVALUATING THE NEUROPROTECTIVE POTENTIAL OF AQUEOUS ASPALATHUS LINEARIS (ROOIBOS) LEAF EXTRACT ON MERCURY CHLORIDE-INDUCED TOXICITY IN THE CEREBELLUM OF ADULT WISTAR RATS

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ABSTRACT
Mercury is a common element in the environment that causes oxidative stress in those who are exposed, which in turn causes tissue damage. The role of natural antioxidants, especially those derived from plants is gaining a lot of attention with scientific evidence showing that vegetables, fruits and teas have protective effects and promote good health. Aspalathus linearis, commonly known as Rooibos, is well known for its rich content of different compounds with antioxidant properties. Studies have shown that it has anticarcinogenic, antimutagenic, anti-diabetic, antioxidant, cardio-protective effects. In this study, the neuroprotective activities of Aspalathus linearis (rooibos) was investigated in mercury chloride-induced neurotoxicity in experimental animals. Forty two adult Wistar rats, which weighed an average of 161g, were used for this study. The rats were grouped into seven groups (A, B, C, D, E, F and G), of six rats each. Group A served as the control and were given 1ml of sterile water, Group B (HgCl2) were given 4mg/kg bodyweight of Mercury chloride only, Group C (RBT + HgCl2) were administered 250mg/kg bodyweight aqueous leaf extract of Aspalathus linearis and 4mg/kg bodyweight of Mercury chloride, Group D (RBT + HgCl2) were administered 500mg/kg bodyweight aqueous leaf extract of Aspalathus linearis and 4mg/kg bodyweight of Mercury chloride, Group E (RBT) were administered 500mg/kg bodyweight aqueous leaf extract of Aspalathus linearis only, Group F (Vit E + HgCl2) were administered 500mg/kg bodyweight of vitamin E and 4mg/kg bodyweight of Mercury chloride and Group G(Vit E) were administered 500mg/kg bodyweight of vitamin E only. All administrations were given orally, through an orogastric tube and the experiment lasted for 28 days. At the end of the study period, the rats were weighed and open field test was performed. The rats were euthanized through cervical dislocation and their brains dissected out. Brain weight was recorded and antioxidant parameters such as MDA, GPx and SOD was investigated. Histology of the cerebellum was also examined in all groups. Result shows, in the neurobehavoural activity, for rearing and ambulation a decrease (P < 0.05) was observed in group B when compared with control, however in rearing and ambulation an increase (P > 0.05) was observed in group C, D and F when compared with group B. For grooming and immobility an increase (P > 0.05) was observed in group B when compared with control, however in grooming and immobility a decrease (P < 0.05) was observed in group C, D and F when compared with group B. Result for antioxidant activity showed oxidative stress ( low antioxidant activity) in group B whereas the Control, RBT and Vit. E groups increase in antioxidant activity. Result from histology showed degeneration of the purkinje cells in the purkinje cell layer of the cerebellum in group B when compared with control, however treatment with RBT and Vit. E reversed the effect. In conclusion the findings showed Aspalathus linearis (rooibos) help to attenuate the neurotoxic effect of mercury-chloride on the cerebellum of adult Wistar rat

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