title: Impaired redox state and respiratory chain enzyme activities in the cerebellum of vitamin A-treated rats.
abstract: Vitamin A is a micronutrient that participates in the maintenance of the mammalian cells homeostasis. However, excess of vitamin A, which may be achieved through increased intake of the vitamin either therapeutically or inadvertently, induces several deleterious effects in a wide range of mammalian cells, including neuronal cells. Vitamin A is a redox-active molecule, and it was previously demonstrated that it induces oxidative stress in several cell types. Therefore, in the present work, we investigated the effects of vitamin A supplementation at clinical doses (1000-9000IU/(kgday)) on redox environment and respiratory chain activity in the adult rat cerebellum. Glutathione-S-transferase (GST) enzyme activity was also measured here. The animals were treated for 3, 7, or 28 days with vitamin A as retinol palmitate. We found increased levels of molecular markers of oxidative damage in the rat cerebellum in any period analyzed. Additionally, vitamin A supplementation impaired cerebellar mitochondrial electron transfer chain (METC) activity. GST enzyme activity was increased in the cerebellum of rats chronically treated with vitamin A. Based on our results and data previously published, we recommend more caution in prescribing vitamin A at high doses even clinically, since there is a growing concern regarding toxic effects associated to vitamin A intake.
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: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D004224:Diterpenes; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D000084562:Retinyl Esters; D013482:Superoxide Dismutase / Q000378:metabolism; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004224:Diterpenes; D045222:Electron Transport Chain Complex Proteins; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D009249:NADP; D013482:Superoxide Dismutase; D005982:Glutathione Transferase