De Oliveira Marcos Roberto, Moreira José Cláudio Fonseca
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.
Toxicology. 2008 Nov 20;253(1-3):125-30. doi: 10.1016/j.tox.2008.09.003. Epub 2008 Sep 10.
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.
维生素A是一种参与维持哺乳动物细胞内稳态的微量营养素。然而，过量的维生素A（可通过治疗性或意外增加维生素摄入量来实现）会在包括神经元细胞在内的多种哺乳动物细胞中引发多种有害影响。维生素A是一种具有氧化还原活性的分子，先前已证明它会在多种细胞类型中诱导氧化应激。因此，在本研究中，我们研究了临床剂量（1000 - 9000IU/（kg·天））的维生素A补充对成年大鼠小脑氧化还原环境和呼吸链活性的影响。此处还测量了谷胱甘肽 - S - 转移酶（GST）的酶活性。动物用视黄醇棕榈酸酯形式的维生素A处理3、7或28天。我们发现在任何分析时间段内，大鼠小脑中氧化损伤的分子标志物水平均升高。此外，补充维生素A会损害小脑线粒体电子传递链（METC）的活性。长期用维生素A处理的大鼠小脑中GST酶活性增加。基于我们的研究结果和先前发表的数据，我们建议即使在临床应用中，高剂量使用维生素A时也应更加谨慎，因为人们越来越关注与维生素A摄入相关的毒性作用。
