Upregulation of Caspase-3 and TNF-α in a rat model of cerebellar motor disorder: role of Cucumis sativus (cucumber).

Cerebellar Motor Disorders (CMDs) are characterized by unsteady gait and uncoordinated movements. Reports indicate that CMDs are caused by congenital malformations, hereditary ataxia, and heavy metal exposure, such as Lead. The antioxidant-rich nature of plants, such as Cucumis sativus (Cucumber), has been well-documented. Accordingly, this study investigated the protective activity of aqueous Cucumis sativus fruit extract (CS) in a lead acetate (Pb) rat model of CMD. Forty Wistar rats (n = 8) were randomly assigned into five groups and treated for twenty-eight days as follows: Group A served as control; Group B received 100 mg/kg body weight (bw) of Pb; Group C received 500 mg/kg bw of CS and Pb; Group D received 1000 mg/kg bw of CS and Pb; Group E received 200 mg/kg bw of Vitamin-E and Pb. Thereafter, neurobehavioral activities, antioxidant enzymes, lipid peroxidation, nitric oxide, Pb concentration, Caspase-3, TNF-α, and cerebella histology were evaluated. Findings revealed that Pb-exposed rats demonstrated significant (p < 0.05) weight loss, impaired motor functions, dysregulated antioxidant enzymes activity, increased lipid peroxidation, elevated cerebellar nitric oxide and Pb concentration, as well as degenerating Purkinje cells and vacuolations in the cerebellum. Also, a significant upregulation (p < 0.05) of Caspase-3 and TNF-α was observed in the cerebella of Pb-exposed rats. However, pretreatment with CS mitigated (p < 0.05) these adverse effects induced by Pb. Taken together, this study offers novel insights into the role of CS as a promising neuroprotective agent and provides translational research evidence demonstrating that CS can be further developed into drugs useful against CMDs.