Background: Parkinson's disease (PD) is characterized by the progressive destruction of dopaminergic nigrostestrial neurons, and the biochemical mechanisms involved in its progression include oxidative stress, neuroinflammation, mitochondrial dysfunction, protein aggregation, excitotoxicity and apoptosis. Current treatment is restricted to symptomatic relief, as there are no agents to prevent neuronal degeneration, which highlights the importance of new substances that could prevent the disease progression. Hesperidin (HSP) is a flavonoid present in most citrus fruits, which has antioxidant and anti-inflammatory properties. In this context, this study aimed to investigate the effects of HSP on the experimental model of PD induced by lipopolysaccharide (LPS).
Methods: Rats unilaterally injured in the right striatum by LPS (2 ?g/animal) were treated with HSP (50, 100 and 200 mg/kg) for 14 days, starting one day after surgery. On the 15th day after surgery, the animals were submitted to specific behavioral tests (Open Field Test, Rotarod and Cylinder Test) and were scarified on the next day for the measurement of neurochemical parameters in the brain areas.
Results: In HSP (100 mg/kg and 200 mg/kg) treated rats, imbalance and incoordination on the Rotarod apparatus was recovered, as the mean latency to fall was significantly higher versus untreated rats (SHAM: 116,2 ± 6 s; LPS: 55,3 ± 7,9 s; HSP100: 104,8 ± 16,2 s; HSP200: 104,2 ± 8,4 s). HSP was also able to prevent neurotoxin-induced neurochemical changes by a significant reduction in nitrite/nitrate levels in the striatum, prefrontal cortex and hippocampus, and by a significant decrease in the levels of MDA in the ipsilateral striatum and prefrontal cortex.
Conclusions: These findings demonstrate an antioxidant and neuroprotective effect of hesperidin, possibly acting on the capture of free radicals, attenuating neurotoxic injuries caused by reactive molecules, with important implications for future studies and for the development of new therapeutic strategies for PD.