de Oliveira Marcos Roberto, Moreira José Cláudio Fonseca
Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, RS, Brazil.
Toxicol Lett. 2007 Sep 28;173(3):145-50. doi: 10.1016/j.toxlet.2007.07.002. Epub 2007 Jul 10.
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.
维生素A是正常脑功能所必需的微量营养素。然而，即使是治疗剂量下高剂量使用维生素A也日益受到关注。在此，我们表明，急性和慢性补充维生素A会对从大鼠大脑皮层和小脑中分离出的亚线粒体颗粒（SMP）诱导氧化应激。治疗剂量（1000 IU/kg或2500 IU/kg）或过量剂量（4500 IU/kg或9000 IU/kg）的慢性和急性维生素A补充均会诱导大脑皮层和小脑SMP中的脂质过氧化、蛋白质羰基化以及蛋白质硫醇基团的氧化。此外，补充维生素A会导致超氧阴离子（O₂⁻）生成增加，表明电子传递链（ETC）发生解偶联。与大脑皮层和小脑相关的运动和探索活动也受到急性和慢性维生素A补充的影响。维生素A导致运动和探索行为均减少。总之，这些结果表明维生素A在亚细胞水平可能具有毒性，会诱导线粒体功能障碍并改变依赖大脑皮层和/或小脑的行为。
