Efeito protetor da hesperidina em um modelo da doença de parkinson induzida por 6-hidroxidopamina em camundongos

Abstract

Parkinson's disease (PD) is a chronic neurodegenerative disorder which has as main characteristic neuropathological depletion of dopamine (DA) striatal. This loss of DA leads to the onset of motor symptoms, such as postural instability, resting tremor, rigidity, bradykinesia, among others. It is a multifactorial disease in age-related, genetic and environmental factors. There is a large evidences correlating oxidative stress with the DP, where there is an imbalance between the generation of reactive species (RS) and cellular defense mechanisms, and it is this imbalance that leads to premature aging, cell death and development of neurodegenerative disorders. Studies show that consumption of a diet rich in flavonoids can reduce the incidence and symptoms of neurodegenerative diseases. The objective of this study was to investigate the effect of administration of the flavonoid hesperidin on behavior in tests of memory, depression, and markers of oxidative stress in a model of PD induced by 6-hydroxydopamine (6-OHDA) in mice eighteen months old lineage C57B/6J. The animals were randomly divided into four groups: (1) vehicle / vehicle, (2) 6-OHDA/veículo, (3) vehicle / hesperidin, (4) 6-OHDA/hesperidina. The neurotoxin 6-OHDA or vehicle saline were infused intracerebroventricular (icv) in one concentration (4 mg / 2 ¶ l in 0.9% NaCl 7

with 0.2 mg / uL ascorbic acid). After injection, the mice have had a recovery period of seven days until the start of treatment. The hesperidin or vehicle (50mg/kg) was administered orally (gavage) for 28 days. After this period, the mice were subjected to behavioral tests (locomotion, memory and depression) and euthanasia. The results demonstrate that oral treatment with hesperidin dose of 50 mg / kg was effective in reducing the cognitive deficits, behavior depressive-like; reduced levels of reactive species (RS), the increase of antioxidant enzyme glutathione peroxidase (GPx) and catalase (CAT), and the total non-enzymatic antioxidant defenses (TRAP) and glutathione (GSH), in the prevention an increase of glutathione reductase (GR). Furthermore, the treatment increased the levels of DA, DOPAC and HVA in striatum compared to mice that received no treatment. In conclusion, we suggest that administration with hesperidin was effective in reviewing the cognitive damage and markers of oxidative stress induced by 6-OHDA in mice, which may contribute as an alternative therapy in reducing symptoms of PD.