Probucol Affords Neuroprotection in a 6-OHDA Mouse Model of Parkinson’s Disease

被引:0
作者
Renata Pietsch Ribeiro
Eduardo Luiz Gasnhar Moreira
Danúbia Bonfanti Santos
Dirleise Colle
Alessandra Antunes dos Santos
Kaite Cristiane Peres
Claudia Pinto Figueiredo
Marcelo Farina
机构
[1] Universidade Federal de Santa Catarina,Programa de Pós
[2] Universidade Federal de Santa Catarina,Graduação em Neurociências, Centro de Ciências Biológicas
[3] Instituto Federal de Santa Catarina,Departamento de Bioquímica, Centro de Ciências Biológicas
[4] Universidade Federal do Rio de Janeiro,Departamento Acadêmico de Saúde e Serviço
来源
Neurochemical Research | 2013年 / 38卷
关键词
Probucol; Oxidative stress; Parkinson’s disease; 6-Hydroxydopamine; Therapeutic strategies;
D O I
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中图分类号
学科分类号
摘要
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic nigrostriatal neurons. Although the etiology of the majority of human PD cases is unknown, experimental evidence points to oxidative stress as an early and causal event. Probucol is a lipid-lowering phenolic compound with anti-inflammatory and antioxidant properties that has been recently reported as protective in neurotoxicity and neurodegeneration models. This study was designed to investigate the effects of probucol on the vulnerability of striatal dopaminergic neurons to oxidative stress in a PD in vivo model. Swiss mice were treated with probucol during 21 days (11.8 mg/kg; oral route). Two weeks after the beginning of treatment, mice received a single intracerebroventricular (i.c.v.) infusion of 6-hydroxydopamine (6-OHDA). On the 21st day, locomotor performance, striatal oxidative stress-related parameters, and striatal tyrosine hydroxylase and synaptophysin levels, were measured as outcomes of toxicity. 6-OHDA-infused mice showed hyperlocomotion and a significant decrease in striatal tyrosine hydroxylase (TH) and synaptophysin levels. In addition, 6-OHDA-infused mice showed reduced superoxide dismutase activity and increased lipid peroxidation and catalase activity in the striatum. Notably, probucol protected against 6-OHDA-induced hyperlocomotion and striatal lipid peroxidation, catalase upregulation and decrease of TH levels. Overall, the present results show that probucol protects against 6-OHDA-induced toxicity in mice. These findings may render probucol as a promising molecule for further pharmacological studies on the search for disease-modifying treatment in PD.
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页码:660 / 668
页数:8
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