• Eur. J. Neurosci. · May 2003

    D-2-hydroxyglutaric acid induces oxidative stress in cerebral cortex of young rats.

    • Alexandra Latini, Karina Scussiato, Rafael Borba Rosa, Susana Llesuy, Adriane Belló-Klein, Carlos Severo Dutra-Filho, and Moacir Wajner.
    • Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
    • Eur. J. Neurosci. 2003 May 1; 17 (10): 2017-22.

    AbstractLarge amounts of d-2-hydroxyglutaric acid (DGA) accumulate in d-2-hydroxyglutaric aciduria (D-2-OHGA), an inherited neurometabolic disorder characterized by severe neurological dysfunction and cerebral atrophy. Despite the significant brain abnormalities, the neurotoxic mechanisms of brain injury in this disease are virtually unknown. In this work, the in vitro effect of DGA on various parameters of oxidative stress was investigated; namely chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR) and the activities of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase in cerebral cortex from 30-day-old-rats. DGA significantly increased chemiluminescence and TBA-RS and decreased TAR values in the cortical supernatants. In contrast, TRAP and the antioxidant enzyme activities were not altered by the metabolite. Furthermore, the DGA-induced increase of TBA-RS was fully prevented by the free radical scavengers ascorbic acid plus Trolox (water-soluble alpha-tocopherol) and attenuated by the inhibitor of nitric oxide synthase Nomega-nitro-L-arginine methyl ester (L-NAME), suggesting the role of superoxide, hydroxyl and nitric oxide radicals in this action. The data indicate a stimulation of lipid peroxidation through the production of free radicals and a reduction of the brain capacity to efficiently modulate the damage associated with the enhanced generation of free radicals by DGA. In the case that these findings also occur in human D-2-OHGA, it is feasible that oxidative stress may be involved in the pathophysiology of the brain injury observed in patients with this disease.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…