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.
de Oliveira
Marcos Roberto
MR
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
de Bittencourt Pasquali
Matheus Augusto
MA
Silvestrin
Roberta Bristot
RB
Mello E Souza
Tadeu
T
Moreira
José Cláudio Fonseca
JC
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