Original Paper

Neurochemical Research

, Volume 38, Issue 3, pp 660-668

First online:

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

  • Renata Pietsch RibeiroAffiliated withPrograma de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa CatarinaDepartamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa CatarinaDepartamento Acadêmico de Saúde e Serviço, Instituto Federal de Santa Catarina Email author 
  • , Eduardo Luiz Gasnhar MoreiraAffiliated withPrograma de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa CatarinaDepartamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina
  • , Danúbia Bonfanti SantosAffiliated withDepartamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina
  • , Dirleise ColleAffiliated withDepartamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina
  • , Alessandra Antunes dos SantosAffiliated withDepartamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina
  • , Kaite Cristiane PeresAffiliated withDepartamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina
  • , Claudia Pinto FigueiredoAffiliated withDepartamento de Fármacos, Faculdade de Farmácia, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro
  • , Marcelo FarinaAffiliated withPrograma de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa CatarinaDepartamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina Email author 

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Abstract

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.

Keywords

Probucol Oxidative stress Parkinson’s disease 6-Hydroxydopamine Therapeutic strategies