title: Evaluation of the effects of vitamin A supplementation on adult rat substantia nigra and striatum redox and bioenergetic states: mitochondrial impairment, increased 3-nitrotyrosine and alpha-synuclein, but decreased D2 receptor contents.
abstract: Vitamin A at moderate to high doses is applied in the treatment of some life threatening pathological conditions, for instance cancers. Additionally, vitamin A at low concentrations is a known antioxidant molecule. However, by increasing vitamin A (or its derivatives) concentrations, there is an increase in the levels of oxidative stress markers in several experimental models. Furthermore, it was reported that vitamin A therapy at high doses might induce cognitive decline among the patients, which may become anxious or depressive, for example, depending on vitamin A levels intake. We have previously reported increased levels of oxidative stress markers in rat substantia nigra and striatum. However, the mechanism by which this vitamin altered the redox environment in such rat brain regions remains to be elucidated. In the herein presented work, we have investigated the effects of vitamin A supplementation at clinical doses (1000-9000 IU/kg day(-1)) for 28 days on rat substantia nigra and striatum mitochondrial electron transfer chain (METC) activity, which may produce superoxide anion radical (O(2)(-*)) when impaired. Additionally, the levels of non-enzymatic antioxidant defenses were evaluated, as well as 3-nitrotyrosine, alpha- and beta-synucleins and TNF-alpha levels through ELISA assay. We observed impaired METC in both rat brain regions. Moreover, we found increased O(2)(-*) production and nitrotyrosine content in the nigrostriatal axis of vitamin A-treated rats, suggesting that the use of vitamin A at therapeutic doses may be rethought due to this toxic effects found here.
authors.affiliation: Centro de Estudos em Estresse Oxidativo (Lab. 32), Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. mrobioq@yahoo.com.br
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: de Oliveira
authors.forename: Max William Soares
authors.initials: MW
authors.lastname: Oliveira
authors.forename: Guilherme Antônio
authors.initials: GA
authors.lastname: Behr
authors.forename: Mariana Leivas Muller
authors.initials: ML
authors.lastname: Hoff
authors.forename: Ricardo Fagundes
authors.initials: RF
authors.lastname: da Rocha
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D019587:Dietary Supplements; D004579:Electron Transport / Q000187:drug effects; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D007202:Indicators and Reagents; D008928:Mitochondria / Q000187:drug effects*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014801:Vitamin A / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D017448:Receptors, Dopamine D2; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D051844:alpha-Synuclein; D014801:Vitamin A; C002744:3-nitrotyrosine; D014443:Tyrosine; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D005982:Glutathione Transferase; D053148:Caspase 3; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III