Impact of Semaglutide and Safinamide versus Bromocriptine on Parkinsonism induced in rats

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by motor impairments such as bradykinesia, rigidity, tremors, and postural instability. Oxidative stress, neuroinflammation, and dopaminergic neuronal loss are key pathological features. Aim: This study aimed to evaluate and compare the neuroprotective effects of semaglutide and safinamide against bromocriptine in a rat model of PD. Materials and Methods: Parkinsonism was induced in rats using rotenone. Animals were divided into eight groups: control, DMSO, bromocriptine (2.5 mg/kg), semaglutide (0.62 mg/kg), safinamide (10 mg/kg), and their respective combinations. Biochemical assays were performed to measure malondialdehyde (MDA), glutathione (GSH), and dopamine levels. Inflammatory cytokines (TNF-α, IL-6) were analyzed. Behavioral tests assessed motor function. Histopathological and immunohistochemical evaluations, including caspase-3 expression, were conducted. Results: All treated groups showed significant improvements in oxidative stress parameters, dopamine restoration, and inflammatory cytokine reduction. Behavioral performance improved across all drug-treated groups, with combined therapies yielding superior outcomes. The bromocriptine + safinamide group exhibited the greatest neuroprotective and functional recovery effects. Conclusion: Bromocriptine, semaglutide, and safinamide, either alone or in combination, demonstrated therapeutic efficacy in rotenone-induced Parkinsonism in rats. Combination therapies, particularly bromocriptine + safinamide, showed enhanced neuroprotective benefits, suggesting a promising strategy for PD management.