Efeito neuroprotetor da hesperidina em modelo de doença de Parkinson induzido por injeção intranigral de LPS em ratos

Abstract

Parkinson's disease (PD) is characterized by the progressive destruction of dopaminergic nigrostestrial neurons. Although the pathophysiology of PD is still not well established, there are some mechanisms involved in its progression that 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. Therefore, the discovery of new substances that could prevent the progression of the disease and reduce the adverse effects of conventional drugs is of paramount importance. 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 hesperidin on the experimental model of PD induced by lipopolysaccharide (LPS). For this, LPSinjured rats (2 μg / animal) unilaterally in the right striatum 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). The results demonstrate that treatment with hesperidin (100 mg / kg i.p) was able to significantly increase the amount of groomings compared to the LPS group. It was also possible to observe a neuroprotective effect in vivo in the recovery of motor damage, such as increased latency time and residence time, parameters evaluated in the rotarod test. However, treatment with HSP did not alter the behavior of the animals in the cylinder test. The compound was also able to prevent neurotoxin-induced neurochemical changes by reducing nitrite/nitrate levels in the striatum, prefrontal cortex and hippocampus, and reduced levels of MDA in the ipsilateral striatum and prefrontal cortex. 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 its application for the development of new therapeutic strategies for PD.