Cellular and Molecular Neurobiology

, Volume 38, Issue 8, pp 1505–1516 | Cite as

Oxidative Imbalance, Nitrative Stress, and Inflammation in C6 Glial Cells Exposed to Hexacosanoic Acid: Protective Effect of N-acetyl-l-cysteine, Trolox, and Rosuvastatin

  • Desirèe Padilha MarchettiEmail author
  • Luiza Steffens
  • Carlos E. Jacques
  • Gilian B. Guerreiro
  • Caroline P. Mescka
  • Marion Deon
  • Daniella M. de Coelho
  • Dinara J. Moura
  • Alice G. Viario
  • Fernanda Poletto
  • Adriana S. Coitinho
  • Laura B. Jardim
  • Carmen R. VargasEmail author
Original Research


X-linked adrenoleukodystrophy (X-ALD) is an inherited neurometabolic disorder caused by disfunction of the ABCD1 gene, which encodes a peroxisomal protein responsible for the transport of the very long-chain fatty acids from the cytosol into the peroxisome, to undergo β-oxidation. The mainly accumulated saturated fatty acids are hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0) in tissues and body fluids. This peroxisomal disorder occurs in at least 1 out of 20,000 births. Considering that pathophysiology of this disease is not well characterized yet, and glial cells are widely used in studies of protective mechanisms against neuronal oxidative stress, we investigated oxidative damages and inflammatory effects of vesicles containing lecithin and C26:0, as well as the protection conferred by N-acetyl-l-cysteine (NAC), trolox (TRO), and rosuvastatin (RSV) was assessed. It was verified that glial cells exposed to C26:0 presented oxidative DNA damage (measured by comet assay and endonuclease III repair enzyme), enzymatic oxidative imbalance (high catalase activity), nitrative stress [increased nitric oxide (NO) levels], inflammation [high Interleukin-1beta (IL-1β) levels], and induced lipid peroxidation (increased isoprostane levels) compared to native glial cells without C26:0 exposure. Furthermore, NAC, TRO, and RSV were capable to mitigate some damages caused by the C26:0 in glial cells. The present work yields experimental evidence that inflammation, oxidative, and nitrative stress may be induced by hexacosanoic acid, the main accumulated metabolite in X-ALD, and that antioxidants might be considered as an adjuvant therapy for this severe neurometabolic disease.


X-linked adrenoleukodystrophy Glial cells N-acetyl-l-cysteine Rosuvastatin Trolox 



Bone marrow transplant




Docosanoic acid


Tetracosanoic acid


Hexacosanoic acid


Heptacosanoic acid


Childhood cerebral form

Endo III

Endonuclease III


Glutathione peroxidase


Hydrogen peroxide










Phosphate buffer saline




Nitric oxide

\({\text{NO}}_{3}^{ - }\)


\({\text{NO}}_{2}^{ - }\)


\({\text{O}}_{2}^{{\cdot - }}\)

Superoxide anion


Standard error of mean




Superoxide dismutase




Very long-chain fatty acid


X-linked adrenoleukodystrophy



This study was supported by Brazilian Foundation Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundo de Incentivo à Pesquisa e Eventos (FIPE/HCPA).

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical Approval

The study was approved by the Ethics Committee of Hospital de Clínicas de Porto Alegre (Number 15-0487).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Desirèe Padilha Marchetti
    • 1
    • 8
    Email author
  • Luiza Steffens
    • 2
  • Carlos E. Jacques
    • 1
  • Gilian B. Guerreiro
    • 3
  • Caroline P. Mescka
    • 3
  • Marion Deon
    • 3
    • 4
  • Daniella M. de Coelho
    • 4
  • Dinara J. Moura
    • 2
  • Alice G. Viario
    • 5
  • Fernanda Poletto
    • 5
  • Adriana S. Coitinho
    • 6
    • 7
  • Laura B. Jardim
    • 4
  • Carmen R. Vargas
    • 1
    • 3
    • 4
    • 8
    Email author
  1. 1.Programa de Pós-Graduação em Ciências Biológicas, BioquímicaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Universidade Federal de Ciências de Saúde de Porto AlegrePorto AlegreBrazil
  3. 3.Programa de Pós-Graduação em Ciências FarmacêuticasUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  4. 4.Serviço de Genética MédicaHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  5. 5.Programa de Pós-Graduação em Química, Instituto de QuímicaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  6. 6.Programa de Pós-Graduação em Ciências Biológicas, Fisiologia, Instituto de Ciências Básicas e da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  7. 7.Programa de Pós-Graduação em Farmacologia e Terapêutica, Instituto de Ciências Básicas e da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  8. 8.Serviço de Genética MédicaHCPAPorto AlegreBrazil

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