title: Increased 3-nitrotyrosine levels in mitochondrial membranes and impaired respiratory chain activity in brain regions of adult female rats submitted to daily vitamin A supplementation for 2 months.
abstract: Vitamin A supplementation among women is a common habit worldwide in an attempt to slow aging progression due to the antioxidant potential attributed to retinoids. Nonetheless, vitamin A elicits a myriad of side effects that result from either therapeutic or inadvertent intake at varying doses for different periods. The mechanism behind such effects remains to be elucidated. In this regard, we performed the present work aiming to investigate the effects of vitamin A supplementation at 100, 200, or 500IU/kgday(-1) for 2 months on female rat brain, analyzing tissue lipid peroxidation levels, antioxidant enzyme activities (both Cu/Zn-superoxide dismutase - SOD - and Mn-SOD); glutathione S-transferase (GST) and monoamine oxidase (MAO) enzyme activity; mitochondrial respiratory chain activity and redox parameters in mitochondrial membranes, as well as quantifying α- and β-synucleins, β-amyloid peptide(1-40), immunoglobulin heavy-chain binding protein/78kDa glucose-regulated protein (BiP/GRP78), receptor for advanced glycation end products (RAGE), D2 receptor, and tumor necrosis factor-α (TNF-α) contents in rat frontal cortex, hippocampus, striatum, and cerebellum. We observed increased lipid peroxidation marker levels, altered Cu/Zn-SOD and Mn-SOD enzyme activities, mitochondrial nitrosative stress, and impaired respiratory chain activity in such brain regions. On the other hand, we did not find any change in MAO and GST enzyme activities, and on α- and β-synucleins, β-amyloid peptide(1-40), GRP78/BiP, RAGE, D2 receptor, and TNF-α contents. Importantly, we did not observed any evidence regarding an antioxidant effect of such vitamin at low doses in this experimental model. The use of vitamin A as an antioxidant therapy among women needs to be reexamined.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. mrobioq@yahoo.com.br
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: de Oliveira
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Lorenzi
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Schnorr
authors.forename: Maurílio
authors.initials: M
authors.lastname: Morrone
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D004579:Electron Transport / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000139:chemically induced*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051843:Synucleins / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism; D014801:Vitamin A / Q000633:toxicity*; D014815:Vitamins / Q000633:toxicity*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D017127:Glycation End Products, Advanced; D017448:Receptors, Dopamine D2; D051843:Synucleins; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D014801:Vitamin A; D014451:Ubiquinone; C002744:3-nitrotyrosine; D014443:Tyrosine; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D008995:Monoamine Oxidase