Acute and chronic vitamin A supplementation at therapeutic doses induces oxidative stress in submitochondrial particles isolated from cerebral cortex and cerebellum of adult rats.
Vitamin A is an essential micronutrient to the normal brain function. However, there is an increasing concern regarding the use of vitamin A at high doses even therapeutically. Here, we show that acute and chronic vitamin A supplementation induces oxidative stress to submitochondrial particles (SMP) isolated from rat cerebral cortex and cerebellum. Both chronic and acute vitamin A supplementation at therapeutic (1000 IU/kg or 2500 IU/kg) or excessive (4500 IU/kg or 9000 IU/kg) doses induced lipid peroxidation, protein carbonylation, and oxidation of protein thiol groups in cerebral cortex and cerebellum SMP. Furthermore, vitamin A supplementation induced an increase in the superoxide (O(2)(-)) anion production, indicating an uncoupling in the electron transfer chain (ETC). Locomotory and exploratory activity, which are associated to cerebral cortex and cerebellum, also were affected by both acute and chronic vitamin A supplementation. Vitamin A induced a decrease in both locomotory and exploratory behavior. Together, these results show that vitamin A could be toxic at the sub cellular level, inducing mitochondrial dysfunction and altering cerebral cortex and/or cerebellum-dependent behavior.
de Oliveira
Marcos Roberto
MR
Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, RS, Brazil. mrobioq@yahoo.com.br
Moreira
José Cláudio Fonseca
JC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D019587:Dietary Supplements / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013367:Submitochondrial Particles / Q000187:drug effects* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014801:Vitamin A / Q000633:toxicity*; D014815:Vitamins / Q000633:toxicity*
D013438:Sulfhydryl Compounds; D014815:Vitamins; D013481:Superoxides; D014801:Vitamin A