title: Vitamin A supplementation at clinical doses induces a dysfunction in the redox and bioenergetics states, but did change neither caspases activities nor TNF-alpha levels in the frontal cortex of adult Wistar rats.
abstract: Vitamin A and its derivatives, the retinoids, exert modulatory roles on central nervous system (CNS) function. However, the clinical use of vitamin A at moderate to high doses induces serious side effects, including dysfunctional brain metabolism and mood disorders. Then, we have investigated in this work the effects of vitamin A supplementation at 1000, 2500, 4500, or 9000IU/kg/day for 28 days on redox and bioenergetics parameters in adult rat frontal cortex. Additionally, we have measured caspase-3 and caspase-8 activities to analyze whether vitamin A supplementation as retinol palmitate induces neuronal death in such brain area. The levels of the pro-inflammatory cytokine TNF-alpha were also quantified. We have found increased rates of O(2)(-) production and increased levels of markers of oxidative insult in frontal cortex and also in mitochondrial membranes. Superoxide dismutase (SOD) enzyme activity was increased, and catalase (CAT) enzyme activity did not change in this experimental model. Surprisingly, we observed increased mitochondrial electron transfer chain (METC) activity. Caspase-3 and caspase-8 activities and TNF-alpha levels did not change in this experimental model. Finally, vitamin A supplementation did not induce depression in adult rats after 28 days of treatment. However, exploration in the center of an open field was decreased and time spent in freezing behavior was increased in vitamin A treated rats.
authors.affiliation: Centro de Estudos em Estresse Oxidativo (Lab. 32), Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 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: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D014801:Vitamin A; D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3; D053181:Caspase 8