ArticleOxidative medicine and cellular longevity2017
Antioxidant Treatment Induces Hyperactivation of the HPA Axis by Upregulating ACTH Receptor in the Adrenal and Downregulating Glucocorticoid Receptors in the Pituitary.
Article in Oxidative medicine and cellular longevity, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
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- Nrf2: A Promising Therapeutic Target for Glucocorticoid-Resistant Chronic Rhinosinusitis.Clinical and experimental otorhinolaryngology · 2026Review
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- The Central Nervous System Modulatory Activities of N-Acetylcysteine: A Synthesis of Two Decades of Evidence.Current issues in molecular biology · 2025Review
- Brain-Targeted Reactive Oxygen Species in Hypertension: Unveiling Subcellular Dynamics, Immune Cross-Talk, and Novel Therapeutic Pathways.Antioxidants (Basel, Switzerland) · 2025Review
- Activation of the Nrf2/HO-1 pathway restores N-acetylcysteine-induced impairment of the hypothalamus-pituitary-adrenal axis negative feedback by up-regulating GRα expression and down-regulating GRβ expression into pituitary glands.Frontiers in endocrinology · 2025Article
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- Induction of Thymus Atrophy and Disruption of Thymocyte Development by Fipronil through Dysregulation of IL-7-Associated Genes.Chemical research in toxicology · 2024Article
- Dimethyl Fumarate Prevents the Development of Chronic Social Stress-Induced Hypertension in Borderline Hypertensive Rats.Antioxidants (Basel, Switzerland) · 2024Article
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- Systems redox biology in health and disease.EXCLI journal · 2022Review
- Increased levels of cortisol are associated with the severity of experimental visceral leishmaniasis in a Leishmania (L.) infantum-hamster model.PLoS neglected tropical diseases · 2021Article
- Neurotoxic Effect of Fipronil in Male Wistar Rats: Ameliorative Effect of L-Arginine and L-Carnitine.Biology · 2021Article
- The Role and Mechanism of Oxidative Stress and Nuclear Receptors in the Development of NAFLD.Oxidative medicine and cellular longevity · 2021Review
- The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.Frontiers in neuroscience · 2021Article
- Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas.Frontiers in pharmacology · 2021Article
- Effects of Xiaoyaosan on Depressive-Like Behaviors in Rats With Chronic Unpredictable Mild Stress Through HPA Axis Induced Astrocytic Activities.Frontiers in psychiatry · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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