Fasudil Improves Motor Functions Against Rotenone-Induced Neurotoxicity in Rats

Abstract

Parkinson’s disease (PD), the second most frequent neurodegenerative disease, involves the
progressive loss of dopaminergic neurons in the substantia Nigra, resulting in motor dysfunction. Recently, Rho-
associated protein kinase (ROCK) has been associated with Parkinson’s pathology. Fasudil (FSD), a ROCK
inhibitor, offers neuroprotection; however, its precise mechanism remains to be explored in the rotenone (ROT)-
exposed animal model. Objectives: This study aimed to evaluate the therapeutic effectiveness of FSD in mitigating
ROT -induced neurotoxicity by attenuating oxidative stress (OS) in a Parkinsonian rat model. Materials and
Methods: Wistar rats were exposed to ROT (2.5 mg/kg; i.p.,) for 28 days to induce Parkinson’s-like symptoms.
Subsequently, FSD (10 mg/kg; p.o.) was administered daily for 28 days in the treatment group. The behavioral
and biochemical assessments were conducted to evaluate motor functions, OS, dopamine (DA) levels, and
mitochondrial functions. Results: Administration of ROT caused increased motor dysfunction and OS, along with
a reduction in dopaminergic content. FSD treatment reversed the motor and biochemical impairments caused by
ROT by restoring DA levels, enhancing enzymatic antioxidant activity, and reducing lipid peroxidation, thereby
protecting dopaminergic neurons. Conclusion: The present study demonstrated that FSD has a neuroprotective
effect in ROT -induced neurotoxicity, mediated by inhibiting the ROCK pathway, which results in the restoration
of antioxidant and DA levels.