Vitamin A supplementation at pharmacological doses induces nitrosative stress on the hypothalamus of adult Wistar rats.
Vitamin A is a micronutrient involved in the regulation of a normal mammalian brain function. In spite of this, it has been demonstrated that vitamin A exerts a wide range of deleterious effects regarding neuronal homeostasis, for instance impairing brain metabolism and suppressing neurogenesis, to cite a few. In addition, vitamin A is a redox active molecule, i.e. it is both anti- and pro-oxidant, depending on its concentration. In the herein presented work, we performed some experiments aiming to investigate the effects of clinically applied doses of vitamin A (1000-9000 IU/kg/day during 28 days) on rat hypothalamic redox state and mitochondrial electron transfer chain (METC) activity, as well as on hypothalamic alpha-synuclein and D2 receptor (dopamine receptor) contents. Additionally, we quantified caspase-3 activity and tumor necrosis factor-alpha (TNF-alpha) levels to assess either neuronal death or an inflammatory state in such brain area. We found that vitamin A supplementation increased free radical production, as well as oxidative and nitrosative stress, in rat hypothalamus. Also, we observed increased complex I-III activity, but decreased complex IV activity in the hypothalamus of vitamin A-treated rats, which may give rise to the increased superoxide anion (O(2)(-)) production found here. Other parameters investigated here, i.e. alpha-synuclein and D2 receptor contents did not change. Even though we did not observe signs of increased cell death or inflammation in the rat hypothalamus, more attention is needed when vitamin A is the choice of treatment in certain pathologies.
De Oliveira
Marcos Roberto
MR
Centro de Estudos em Estresse Oxidativo (Lab. 32), Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. mrobioq@yahoo.com.br
Oliveira
Max William Soares
MW
Da Rocha
Ricardo Fagundes
RF
Moreira
José Cláudio Fonseca
JC
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D014801:Vitamin A / Q000008:administration & dosage*; D051844:alpha-Synuclein / Q000378:metabolism
D045222:Electron Transport Chain Complex Proteins; D017448:Receptors, Dopamine D2; D014409:Tumor Necrosis Factor-alpha; D051844:alpha-Synuclein; D013481:Superoxides; D014801:Vitamin A; C002744:3-nitrotyrosine; D014443:Tyrosine; D053148:Caspase 3