ABSTRACT

Nickel chloride (NiCl₂) exposure poses a significant threat to neurological health, particularly cerebellar function. This study aimed to investigate the potential mitigating role of rutin, a flavonoid with potent antioxidant properties, against NiCl₂ -induced cerebellar toxicity in Wistar rats. Forty-two (42) Wistar rats were purchased, acclimatized, weighed and divided into six groups: Group A-F. The rats in Group A (Control) received distilled water only. The rats in Group B (NiCl₂) received Nickel-Chloride only at 5mg/kg. Groups C was administered Rutin and Nickel at 50 mg/kg and 5 mg/kg body weight respectively. Group D received Rutin and Nickel-chloride at 100mg/kg and 5mg/kg respectively. Group E and Group F were administered 50mg/kg and 100 mg/kg of Rutin only respectively. Rutin and Nickel-Chloride were administered orally (through an orogastric tube) and intraperitoneally respectively for twenty-eight (28) days. During the entire study period, all rats were allowed free access to water and fed with standard rat chow. Rutin pretreatment was done an hour before NiCl₂ administration. At the end of the administration, the rats were weighed and the neurobehavioral activity was evaluated using the Open field test. The rats were then sacrificed by cervical dislocation and the cerebellum was harvested for antioxidant enzymes (Catalase and Superoxide Dismutase), gene expression (Nrf2 and caspase 3), and histological evaluation. The results showed that there was significant decrease (P<0.05) in body and organ weight in the groups treated with NiCl₂ only compared to the control group. Rutin administration significantly mitigated NiCl₂-induced neurobehavioral deficits, as evidenced by improved locomotor activity and coordination as opposed to NiCl₂ only group. Histological examination demonstrated a reduction in cerebellar tissue damage and neuronal degeneration in Rutin-pretreated groups when compared to the NiCl₂ -alone group. Furthermore, Rutin pretreatment attenuated oxidative stress by enhancing antioxidant enzymes activity (SOD and CAT), inhibiting lipid peroxidation (MDA), and upregulating NRF2 expression as well as downregulating caspase 3 expression. These findings suggest that Rutin exerted neuroprotective effects against NiCl₂ -induced cerebellar toxicity via the upregulation of NRF2 in experimental rats.