Vitamin A supplementation induces a prooxidative state in the striatum and impairs locomotory and exploratory activity of adult rats.
Although vitamin A has been reported to be essential to brain homeostasis, some central nervous system (CNS)-associated deleterious effects may be induced by vitamin A or by its metabolites. In this work, we investigated the effects of acute and chronic vitamin A supplementation at therapeutic (1,000 or 2,500 IU/kg/day) or excessive (4,500 or 9,000 IU/kg/day) doses on the redox state of the rat striatum. We found a 1.8- to 2.7-fold increase of lipid peroxidation in the striatum after acute or chronic supplementation (TBARS method). Therapeutic doses induced a 1.6- to 2.2-fold increase of protein carbonylation (dinitrophenylhydrazine (DNPH) derivatization). Vitamin A supplementation induced a 1.2- to 1.4-fold decrease of protein thiol content acutely and chronically. Superoxide dismutase (SOD) activity, assessed through the inhibition of epinephrine's autoxidation, was increased in a dose-dependent manner chronically. Acutely, both therapeutic and excessive vitamin A doses induced a 1.8- to 2.2-fold decrease of catalase (CAT) activity, as determined through the rate of decrease of hydrogen peroxide (H(2)O(2)). Glutathione peroxidase (GPx) activity did not change in this experimental model. Some vitamin A doses decreased the non-protein thiol content only chronically. Vitamin A supplementation decreased the striatal non-enzymatic antioxidant defenses (TRAP assay). Furthermore, our results show that vitamin A supplementation impaired the SOD/CAT ratio. Moreover, we observed a 1.6- to 2.0-fold decrease of locomotion and exploration in an open field after vitamin A supplementation. Therefore, our results suggest that vitamin A supplementation induces oxidative stress in the rat striatum and that it may be related to a metabolic impairment in such brain area.
Centro de Estudos em Estresse Oxidativo (Lab. 32), Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. mrobioq@yahoo.com.br
Marcos Roberto
MR
de Oliveira
Matheus Augusto
MA
de Bittencourt Pasquali
Roberta Bristot
RB
Silvestrin
Tadeu
T
Mello E Souza
José Cláudio Fonseca
JC
Moreira
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D001928:Brain Diseases, Metabolic / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D050050:Protein Carbonylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014801:Vitamin A / Q000633:toxicity*
D000975:Antioxidants; D013438:Sulfhydryl Compounds; D014801:Vitamin A; D002374:Catalase; D013482:Superoxide Dismutase