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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 4156361, 10 pages
Research Article

Antioxidant Treatment Induces Hyperactivation of the HPA Axis by Upregulating ACTH Receptor in the Adrenal and Downregulating Glucocorticoid Receptors in the Pituitary

1Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Av. Brasil, No. 4365, Manguinho, 21045-900 Rio de Janeiro, RJ, Brazil
2Laboratório 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, RJ, Brazil
3National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Rio de Janeiro, RJ, Brazil

Correspondence should be addressed to Vinicius F. Carvalho; moc.liamtoh@sairfsuiciniv

Received 10 January 2017; Revised 10 March 2017; Accepted 20 March 2017; Published 21 May 2017

Academic Editor: Ayman M. Mahmoud

Copyright © 2017 Jessika P. Prevatto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Glucocorticoid (GC) production is physiologically regulated through a negative feedback loop mediated by the GC, which appears 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.