Neurotoxicity Research

, Volume 33, Issue 3, pp 580–592 | Cite as

Chronic Mild Hyperhomocysteinemia Alters Inflammatory and Oxidative/Nitrative Status and Causes Protein/DNA Damage, as well as Ultrastructural Changes in Cerebral Cortex: Is Acetylsalicylic Acid Neuroprotective?

  • Daniella de S. Moreira
  • Paula W. Figueiró
  • Cassiana Siebert
  • Caroline A. Prezzi
  • Francieli Rohden
  • Fatima C. R. Guma
  • Vanusa Manfredini
  • Angela T. S. Wyse


Homocysteine is a sulfur-containing amino acid derived from methionine metabolism. When plasma homocysteine levels exceed 10–15 μM, there is a condition known as hyperhomocysteinemia, which occur as a result of an inborn error of methionine metabolism or by non-genetic causes. Mild hyperhomocysteinemia is considered a risk factor for development of neurodegenerative diseases. The objective of the present study was to evaluate whether acetylsalicylic acid has neuroprotective role on the effect of homocysteine on inflammatory, oxidative/nitrative stress, and morphological parameters in cerebral cortex of rats subjected to chronic mild hyperhomocysteinemia. Wistar male rats received homocysteine (0.03 μmol/g of body weight) by subcutaneous injections twice a day and acetylsalicylic acid (25 mg/Kg of body weight) by intraperitoneal injections once a day from the 30th to the 60th postpartum day. Control rats received vehicle solution in the same volume. Results showed that rats subjected to chronic mild hyperhomocysteinemia significantly increased IL-1β, IL-6, and acetylcholinesterase activity and reduced nitrite levels. Homocysteine decreased catalase activity and immunocontent and superoxide dismutase activity, caused protein and DNA damage, and altered neurons ultrastructure. Acetylsalicylic acid totally prevented the effect of homocysteine on acetylcholinesterase activity and catalase activity and immunocontent, as well as the ultrastructural changes, and partially prevented alterations on IL-1β levels, superoxide dismutase activity, sulfhydryl content, and comet assay. Acetylsalicylic acid per se increased DNA damage index. In summary, our findings showed that chronic chemically induced model of mild hyperhomocysteinemia altered some parameters and acetylsalicylic acid administration seemed to be neuroprotective, at least in part, on neurotoxicity of homocysteine.


Homocysteine Hyperhomocysteinemia Acetylsalicylic acid Inflammation Oxidative/nitrative stress Ultrastructural changes 


Funding Information

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil), PRONEX(16/2551-0000465-0)/Fundação de Amparo a Pesquisa do Rio Grande do Sul (FAPERGS-Brazil) and INCT (EN 465671/2014-4)/CNPq-Brazil.

Compliance with Ethical Standards

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed and experimental protocol was approved by the University’s Ethics Committee (CEUA) under the project #31436.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

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

Authors and Affiliations

  • Daniella de S. Moreira
    • 1
    • 2
  • Paula W. Figueiró
    • 1
    • 2
  • Cassiana Siebert
    • 1
    • 2
  • Caroline A. Prezzi
    • 2
  • Francieli Rohden
    • 1
  • Fatima C. R. Guma
    • 1
    • 3
  • Vanusa Manfredini
    • 4
  • Angela T. S. Wyse
    • 1
    • 2
    • 3
  1. 1.Programa de Pós-Graduação em Ciências Biológicas: BioquímicaICBS, UFRGSPorto AlegreBrazil
  2. 2.Laboratório de Neuroproteção e Doenças Neurometabólicas, Departamento de BioquímicaICBS, UFRGSPorto AlegreBrazil
  3. 3.Departamento de BioquímicaICBS, UFRGSPorto AlegreBrazil
  4. 4.Laboratório de Hematologia e Citologia ClínicaUniversidade Federal do PampaUruguaianaBrazil

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