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

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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.

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Acknowledgments

The financial supports by (1) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), (2) IBN.NET/CNPq, (3) PRONEX-CNPq/FAPESC (NENASC project), (4) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and (5) INCT-CNPq-Excitotoxicity and Neuroprotection are gratefully acknowledged. M.F. and C.P.F. are recipients of CNPq fellowships.

Conflict of interest

The authors have no financial or personal conflicts of interest related to this work.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil

    Renata Pietsch Ribeiro, Eduardo Luiz Gasnhar Moreira & Marcelo Farina

  2. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil

    Renata Pietsch Ribeiro, Eduardo Luiz Gasnhar Moreira, Danúbia Bonfanti Santos, Dirleise Colle, Alessandra Antunes dos Santos, Kaite Cristiane Peres & Marcelo Farina

  3. Departamento Acadêmico de Saúde e Serviço, Instituto Federal de Santa Catarina, Florianópolis, Santa Catarina, 88020-030, Brazil

    Renata Pietsch Ribeiro

  4. Departamento de Fármacos, Faculdade de Farmácia, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil

    Claudia Pinto Figueiredo

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  1. Renata Pietsch Ribeiro
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Ribeiro, R.P., Moreira, E.L.G., Santos, D.B. et al. Probucol Affords Neuroprotection in a 6-OHDA Mouse Model of Parkinson’s Disease. Neurochem Res 38, 660–668 (2013). https://doi.org/10.1007/s11064-012-0965-0

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