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Neurotoxicity Research

, Volume 33, Issue 3, pp 549–559 | Cite as

Atorvastatin Prevents Early Oxidative Events and Modulates Inflammatory Mediators in the Striatum Following Intranasal 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Administration in Rats

  • Naiani F. Marques
  • Adalberto A. Castro
  • Gianni Mancini
  • Fernanda L. Rocha
  • Adair R. S. Santos
  • Rui D. Prediger
  • Andreza Fabro De Bem
  • Carla I. Tasca
ORIGINAL ARTICLE
  • 168 Downloads

Abstract

Atorvastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor with cholesterol-lowering, anti-inflammatory, and antioxidant properties. Increasing evidence show atorvastatin acts as a protective agent against insults in the central nervous system (CNS). The regular use of statins has been associated with a reduced risk of Parkinson’s disease (PD) development. Here, we evaluated early events involved in the neurotoxicity induced by intranasal (i.n.) infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rats and the potential of atorvastatin to prevent these early toxic events. Male Wistar rats were pretreated orally with atorvastatin (10 mg/kg/day) or vehicle once a day during seven consecutive days. Twenty-four hours after atorvastatin administration, animals received a single bilateral i.n. infusion of MPTP (1 mg/nostril), and 6 h later, the striatum and the hippocampus were collected to evaluate early oxidative stress parameters and inflammatory cytokines. Atorvastatin prevented MPTP-induced increase in reactive species (RS) generation and in glutathione levels in the striatum. Atorvastatin also prevented the reduction in mitochondrial respiratory chain complex I and II activities evoked by MPTP in the striatum. Atorvastatin per se reduced the levels of the cytokines TNF-α and IL-1β, and surprisingly, it reduced IL-10 and nerve growth factor levels in the striatum. However, the anti-inflammatory IL-10 levels increased in the striatum following atorvastatin plus MPTP treatment. These effects were not observed in the hippocampus. Our findings reinforce and extend the notion of the neuroprotective effects of atorvastatin in a PD model and indicate the modulation of oxidative and inflammatory responses as the mechanisms associated with therapeutic action of atorvastatin in PD.

Keywords

Atorvastatin Parkinson’s disease MPTP Intranasal Oxidative stress Neuroinflammation 

Abbreviations

Ator

Atorvastatin

DCF-DA

2′,7′-Dichlorofluorescein diacetate

GPx

Glutathione peroxidase

GR

Glutathione reductase

GSH

Glutathione

HMG-CoA

3-Hydroxy-3-methylglutaryl coenzyme A

IL-10

Interleukin 10

IL-1β

Interleukin 1 beta

MPTP

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NGF

Nerve growth factor

PD

Parkinson’s disease

RS

Reactive species

SNpc

Substantia nigra pars compacta

TH

Tyrosine hydroxylase

TNF-α

Tumoral necrosis factor alpha

Notes

Author Contribution

All authors have materially participated in the research and/or article preparation.

Funding Information

This work was supported by grants from Brazilian funding agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Programa de Apoio aos Núcleos de Excelência (PRONEX—Project NENASC), Fundação de Apoio à Pesquisa do Estado de Santa Catarina (FAPESC), FINEP (Financiadora de Estudos e Projetos-IBN-Net no. 01.06.0842-00), and INCT (Instituto Nacional de Ciência e Tecnologia) for the excitotoxicity and neuroprotection. CIT, RDP, ARSS, and AFDB are a recipient of CNPq productivity fellowship.

Compliance with Ethical Standards

All procedures performed in this study were in accordance with the animal protocols of institutional ethics committee (CEUA).

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Naiani F. Marques
    • 1
  • Adalberto A. Castro
    • 1
    • 2
  • Gianni Mancini
    • 1
  • Fernanda L. Rocha
    • 3
    • 4
  • Adair R. S. Santos
    • 3
  • Rui D. Prediger
    • 5
  • Andreza Fabro De Bem
    • 1
  • Carla I. Tasca
    • 1
  1. 1.Programa de Pós-Graduação em Bioquímica, Departamento de Bioquímica, Centro de Ciências BiológicasUniversidade Federal de Santa CatarinaFlorianópolisBrazil
  2. 2.Núcleo de Estudos Aplicados a SaúdeCentro Universitário Barriga VerdeOrleansBrazil
  3. 3.Laboratório de Neurobiologida da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências BiológicasUniversidade Federal de Santa CatarinaFlorianópolisBrazil
  4. 4.Curso de Farmácia, Universidade do ContestadoCampus de ConcórdiaConcórdiaBrazil
  5. 5.Departamento de Farmacologia, Centro de Ciências BiológicasUniversidade Federal de Santa CatarinaFlorianópolisBrazil

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