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
immunohistochemical
function.
evaluations,
Histopathological
including
and
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.