ABSTRACT
Aluminium chloride (AlCl3) is a potent neurotoxicant implicated in neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington's disease (HD). These conditions are characterized by memory loss, cognitive decline, and cholinergic deficits. The neurotoxicity of aluminum is reported to cause oxidative damage, apoptosis and irreversible damage to neurons. Since brain cells are particularly sensitive to oxidative damage due to their high oxygen uptake, the regular consumption of antioxidants is important to provide neuroprotection. Ascorbic acid (AA) is a water-soluble vitamin with multiple cellular functions. In humans, dietary supplements are necessary for the intake of ascorbic acid, with fruits and vegetables serving as the primary sources of AA. It acts as a potent antioxidant and a scavenger for free radicals. Accordingly, this study was designed to investigate the antioxidant and anti- cholinesterase activity of Ascorbic acid in the Cerebellum of Wistar rats treated with Aluminium chloride. After purchase and acclimatization, the Wistar rats were weighed and divided into six equal groups (control and treated groups). The six groups contained eight wistar rats each with a total of 48 animals. Group A served as control and received 1 ml of distilled water. Group B received 100 mg/Kg of AlCl3-only. Group C received 100 mg/Kg of AA1 and 100 mg/Kg of AlCl. Group D received 200 mg/Kg of AA2 and 100 mg/Kg of AlCl3. Group E received 100 mg/Kg of AA1 only. Group F received 200 mg/Kg of AA2 only. For twenty-eight days, all administrations were done orally via an orogastric tube. The rats were fed with standard rat chow and had free access to water throughout the duration of the study. At the end of the administration, neurobehavioural activity was recorded and evaluated using the Open field test (OFT). The rats were sacrificed by cervical dislocation and the cerebelli was harvested for antioxidant [Catalase (CAT), Glutathione Peroxidase (GPx), Superoxide Dismutase (SOD), Glutathione (GSH)] and Lipid Peroxidation (MDA) evaluations. Also, the acetylcholinesterase (AChE) activity was evaluated. Routine hematoxylin and eosin staining techniques were utilized to evaluate the histological changes in the cerebelli of the rats. The results showed a significant decrease (p<0.05) in the final body and whole brain weight of rats treated with AlCl3-only in contrast to the control and AA groups which showed a significant increase (p<0.05) in final body and whole brain weight. Results from neurobehavioural activity (Rearing, Grooming, Ambulation, Immobility, Thigmotaxis, Central square entry, Sniffing and Crossing) showed that rats treated with AlCl3-only had significantly reduced (p<0.05) neurobehavioural function compared to the rats in control group and pretreated AA groups. Assessment of antioxidants showed low antioxidant activity and elevated lipid peroxidation in the cerebellum of AlCl3 group whereas in the control and pretreated AA groups there was a significantly higher (p<0.05) antioxidant activity and a lower lipid peroxidation. A high concentration of AChE was observed in the cerebellum of rats treated with AlCl3-only and a low concentration in the cerebellum of rats in the control group and rats pretreated with AA. Histological findings revealed morphological alterations (Shrinkage and degeneration of Purkinje cells, darkly stained and irregular Purkinje cells and vacuolation of the Molecular and Purkinje cell layer) in the cerebellum of AlCl3 group while the pretreated with AA showed similar morphology to the control group. In conclusion, the findings showed that Ascorbic acid was not toxic to the animals but protected against Aluminium chloride toxicity. These findings therefore provide the first research evidence of the neuroprotective activity of Ascorbic acid on Aluminium chlorideinduced cerebellar toxicity in Wistar rats.
