Abstract
Several diseases associated with high-altitude exposure affect unacclimated individuals. These diseases include acute mountain sickness (AMS), high-altitude cerebral edema (HACE), high-altitude pulmonary edema (HAPE), chronic mountain sickness (CMS), and, notably, high-altitude pulmonary hypertension (HAPH), which can eventually lead to right ventricle hypertrophy and heart failure. The development of these pathologies involves different molecules and molecular pathways that might be related to oxidative stress. Studies have shown that acute, intermittent, and chronic exposure to hypobaric hypoxia induce oxidative stress, causing alterations to molecular pathways and cellular components (lipids, proteins, and DNA). Therefore, the aim of this review is to discuss the oxidative molecules and pathways involved in the development of high-altitude diseases. In summary, all high-altitude pathologies are related to oxidative stress, as indicated by increases in the malondialdehyde (MDA) biomarker and decreases in superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant activity. In addition, in CMS, the levels of 8-iso-PGF2α and H2O2 are increased, and evidence strongly indicates an increase in Nox4 activity in HAPH. Therefore, antioxidant treatments seem to be a promising approach to mitigating high-altitude pathologies.
Highlights
In recent years, the number of people with acute, intermittent, or permanent exposure to high altitudes has increased considerably, and it has been estimated that more than 81.6 million people live at altitudes ≥2500 m [1]
Through a proteomic and metabolomics analysis, a recent study on rats with chronic mountain sickness (CMS) induced by 28-day exposure to hypobaric hypoxia reported an increase in 8-hydroxyguanosine and trimethylamine N-oxide, which were associated with oxidative stress and pulmonary vasoconstriction processes, respectively [68]
The link between right ventricular hypertrophy (RVH) and oxidative stress is further supported by a study on rats under chronic hypobaric hypoxia conditions (5475 m; 28 days), which found that pulmonary artery vascular remodeling, RVH, and increased right ventricular systolic pressure occurred by the end of exposure; all of these effects were related to increased H2 O2 and decreased superoxide dismutase (SOD) and GSH levels in the lung [79]
Summary
The number of people with acute, intermittent (shift work; days at high altitude and rest days at sea level, for years), or permanent exposure to high altitudes has increased considerably, and it has been estimated that more than 81.6 million people live at altitudes ≥2500 m [1]. Previous studies have shown that both acute and chronic exposure to hypobaric hypoxia increase the levels of oxidative stress biomarkers [9], highlighting that in certain tissues, such as the lung, oxidative stress is rapidly triggered under high-altitude exposure. A study has shown that within 1.5 h of exposure to acute hypobaric hypoxia, the levels of reactive oxygen species (ROS) and the oxidative stress biomarker malondialdehyde (MDA), a product of lipid peroxidation, increase in the lungs of rats [10]. Antioxidants 2022, 11, 267 have implicated oxidative stress in the development of pathologies induced by hypobaric hypoxia exposure, such as those mentioned above [8,10,12,13,14]. The aim of this review is to discuss the oxidative molecules and pathways involved in the development of acute and chronic mountain sickness, pulmonary and cerebral high-altitude edema, and pulmonary hypertension, because this information is necessary to understand and potentially mitigate these pathologies, by revealing pharmacological targets
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
