ArticleFree radical biology & medicine2013
Nrf2 activation: a potential strategy for the prevention of acute mountain sickness.
Article in Free radical biology & medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses.Pharmaceutical biology · 2021Pooled it
- Pharmacokinetics and pharmacodynamics of the novel Nrf2 activator omaveloxolone in primates.Drug design, development and therapy · 2019Trial
- Topical application of RTA 408 lotion activates Nrf2 in human skin and is well-tolerated by healthy human volunteers.BMC dermatology · 2015Trial
- Ferroptosis, orchestrated by GPX4 downregulation, serves as a critical mediator of neutrophil extracellular trap-driven pathology in hypoxic pulmonary edema.Apoptosis : an international journal on programmed cell death · 2026Article
- Low hypoxia tolerance as a determinant of the proinflammatory phenotype: a trained immunity perspective.Frontiers in immunology · 2026Review
- Eleutheroside E Attenuates Hypobaric Hypoxia-Induced High Altitude Pulmonary Edema by Regulating Ferritinophagy-Mediated Ferroptosis via Keap1-Nrf2 Regulatory Axis.Journal of inflammation research · 2026Article
- Antioxidants Trolox and Methazolamide Protect Microvascular Endothelial Cells from Oxidative Damage Induced by Sporadic and Familial Forms of Oligomeric Amyloid-β.Antioxidants (Basel, Switzerland) · 2025Article
- ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions.Molecular biomedicine · 2025Review
- Alzheimer's Disease Pathogenic Mechanisms: Linking Redox Homeostasis and Mitochondria-Associated Metabolic Pathways Through Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2).Antioxidants (Basel, Switzerland) · 2025Review
- Research developments in the neurovascular unit and the blood‑brain barrier (Review).Biomedical reports · 2025Review
- Niraparib restricts intraperitoneal metastases of ovarian cancer by eliciting CD36-dependent ferroptosis.Redox biology · 2025Article
- Eleutheroside B Ameliorates Cardiomyocytes Necroptosis in High-Altitude-Induced Myocardial Injury via Nrf2/HO-1 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Article
- Role of intermittent hypoxic training combined with methazolamide in the prevention of high-altitude cerebral edema in rats.Scientific reports · 2024Article
- Network pharmacology andHeliyon · 2024Article
- Protective effects of epigallocatechin-3-gallate counteracting the chronic hypobaric hypoxia-induced myocardial injury in plain-grown rats at high altitude.Cell stress & chaperones · 2023Article
- Dental Pulp-Derived Stem Cells Preserve Astrocyte Health During Induced Gliosis by Modulating Mitochondrial Activity and Functions.Cellular and molecular neurobiology · 2023Article
- FDA approved L-type channel blocker Nifedipine reduces cell death in hypoxic A549 cells through modulation of mitochondrial calcium and superoxide generation.Free radical biology & medicine · 2021Article
- Role of Carbonic Anhydrase in Cerebral Ischemia and Carbonic Anhydrase Inhibitors as Putative Protective Agents.International journal of molecular sciences · 2021Review
- Understanding the role of the cytoprotective transcription factor nuclear factor erythroid 2-related factor 2-lessons from evolution, the animal kingdom and rare progeroid syndromes.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Reactive oxygen species (ROS) formed during acute high altitude exposure contribute to cerebral vascular leak and development of acute mountain sickness (AMS). Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) is a transcription factor that regulates expression of greater than 90% of antioxidant genes, but prophylactic treatment with Nrf2 activators has not yet been tested as an AMS therapy. We hypothesized that prophylactic activation of the antioxidant genome with Nrf2 activators would attenuate high-altitude-induced ROS formation and cerebral vascular leak and that some drugs currently used to treat AMS symptoms have an additional trait of Nrf2 activation. Drugs commonly used to treat AMS were screened with a luciferase reporter cell system for their effectiveness to activate Nrf2, as well as being tested for their ability to decrease high altitude cerebral vascular leak in vivo. Compounds that showed favorable results for Nrf2 activation from our screen and attenuated high altitude cerebral vascular leak in vivo were further tested in brain microvascular endothelial cells (BMECs) to determine if they attenuated hypoxia-induced ROS production and monolayer permeability. Of nine drugs tested, with the exception of dexamethasone, only drugs that showed the ability to activate Nrf2 (Protandim, methazolamide, nifedipine, amlodipine, ambrisentan, and sitaxentan) decreased high-altitude-induced cerebral vascular leak in vivo. In vitro, Nrf2 activation in BMECs before 24h hypoxia exposure attenuated hypoxic-induced hydrogen peroxide production and permeability. Prophylactic Nrf2 activation is effective at reducing brain vascular leak from acute high altitude exposures. Compared to acetazolamide, methazolamide may offer better protection against AMS. Nifedipine, in addition to its known vasodilatory activities in the lung and protection against high altitude pulmonary edema, may provide protection against brain vascular leak as well.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.