Chronic mild Hyperhomocysteinemia impairs energy metabolism, promotes DNA damage and induces a Nrf2 response to oxidative stress in rats brain
| Autor: | Angela T. S. Wyse, Tiago Marcon dos Santos, Vanusa Manfredini, Cassiana Siebert, Micaela Federizzi de Oliveira |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Antioxidant Homocysteine NF-E2-Related Factor 2 DNA damage medicine.medical_treatment Hyperhomocysteinemia Prefrontal Cortex medicine.disease_cause Models Biological Antioxidants Superoxide dismutase 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Cytochrome c oxidase Rats Wistar Cell Nucleus chemistry.chemical_classification biology Chemistry Glutathione peroxidase Brain Cell Biology General Medicine Amygdala Oxidative Stress 030104 developmental biology Endocrinology Catalase Chronic Disease biology.protein Energy Metabolism 030217 neurology & neurosurgery Oxidative stress DNA Damage |
| Zdroj: | Cellular and Molecular Neurobiology. 39:687-700 |
| ISSN: | 1573-6830 0272-4340 |
| DOI: | 10.1007/s10571-019-00674-8 |
| Popis: | Homocysteine (HCY) has been linked to oxidative stress and varied metabolic changes that are dependent on its concentration and affected tissues. In the present study we evaluate parameters of energy metabolism [succinate dehydrogenase (SDH), complex II and IV (cytochrome c oxidase), and ATP levels] and oxidative stress [DCFH oxidation, nitrite levels, antioxidant enzymes and lipid, protein and DNA damages, as well as nuclear factor erythroid 2-related (Nrf2) protein abundance] in amygdala and prefrontal cortex of HCY-treated rats. Wistar male rats were treated with a subcutaneous injection of HCY (0.03 µmol/g of body weight) from the 30th to 60th post-natal day, twice a day, to induce mild hyperhomocysteinemia (HHCY). The rats were euthanatized without anesthesia at 12 h after the last injection, and amygdala and prefrontal cortex were dissected for biochemical analyses. In the amygdala, mild HHCY increased activities of SDH and complex II and decreased complex IV and ATP level, as well as increased antioxidant enzymes activities (glutathione peroxidase and superoxide dismutase), nitrite levels, DNA damage, and Nrf 2 protein abundance. In the prefrontal cortex, mild HHCY did not alter energy metabolism, but increased glutathione peroxidase, catalase and DNA damage. Other analyzed parameters were not altered by HCY-treatment. Our findings suggested that chronic mild HHCY changes each brain structure, particularly and specifically. These changes may be associated with the mechanisms by which chronic mild HHCY has been linked to the risk factor of fear, mood disorders and depression, as well as in neurodegenerative diseases. |
| Databáze: | OpenAIRE |
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