Prevatto Jessika P, Torres Rafael C, Diaz Bruno L, Silva Patrícia M R E, Martins Marco A, Carvalho Vinicius F
Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Av. Brasil, No. 4365, Manguinho, 21045-900 Rio de Janeiro, Brazil.
Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, No. 373, Cidade Universitária-Ilha do Fundão, 21941-902 Rio de Janeiro, Brazil.
Oxid Med Cell Longev. 2017;2017:4156361. doi: 10.1155/2017/4156361. Epub 2017 May 9.
Glucocorticoid (GC) production is physiologically regulated through a negative feedback loop mediated by the GC, which appear disrupted in several pathological conditions. The inability to perform negative feedback of the hypothalamus-pituitary-adrenal (HPA) axis in several diseases is associated with an overproduction of reactive oxygen species (ROS); however, nothing is known about the effects of ROS on the functionality of the HPA axis during homeostasis. This study analyzed the putative impact of antioxidants on the HPA axis activity and GC-mediated negative feedback upon the HPA cascade. Male Wistar rats were orally treated with N-acetylcysteine (NAC) or vitamin E for 18 consecutive days. NAC-treated rats were then subjected to a daily treatment with dexamethasone, which covered the last 5 days of the antioxidant therapy. We found that NAC and vitamin E induced an increase in plasma corticosterone levels. NAC intensified MC2R and StAR expressions in the adrenal and reduced GR and MR expressions in the pituitary. NAC also prevented the dexamethasone-induced reduction in plasma corticosterone levels. Furthermore, NAC decreased HO-1 and Nrf2 expression in the pituitary. These findings show that antioxidants induce hyperactivity of the HPA axis via upregulation of MC2R expression in the adrenal and downregulation of GR and MR in the pituitary.
糖皮质激素（GC）的产生在生理上是通过由GC介导的负反馈回路进行调节的，而在几种病理状态下这种调节似乎受到了破坏。在几种疾病中，下丘脑-垂体-肾上腺（HPA）轴无法进行负反馈与活性氧（ROS）的过量产生有关；然而，关于稳态期间ROS对HPA轴功能的影响却一无所知。本研究分析了抗氧化剂对HPA轴活性以及GC对HPA级联反应介导的负反馈的潜在影响。雄性Wistar大鼠连续18天口服N-乙酰半胱氨酸（NAC）或维生素E。然后对经NAC处理的大鼠进行为期5天的地塞米松每日治疗，这5天涵盖了抗氧化剂治疗的最后阶段。我们发现NAC和维生素E可使血浆皮质酮水平升高。NAC增强了肾上腺中MC2R和StAR的表达，并降低了垂体中GR和MR的表达。NAC还阻止了地塞米松诱导的血浆皮质酮水平降低。此外，NAC降低了垂体中HO-1和Nrf2的表达。这些发现表明，抗氧化剂通过上调肾上腺中MC2R的表达以及下调垂体中GR和MR的表达来诱导HPA轴的功能亢进。
