High-altitude hypoxia induced reactive oxygen species generation, signaling, and mitigation approaches

Homeostasis between pro-oxidants and anti-oxidants is necessary for aerobic life, which if perturbed and shifted towards pro-oxidants results in oxidative stress. It is generally agreed that reactive oxygen species (ROS) production is accelerated with mountainous elevation, which may play a role in spawning serious health crisis. Exposure to increasing terrestrial altitude leads to a reduction in ambient O₂ availability in cells producing a series of hypoxic oxidative stress reactions and altering the redox balance in humans. Enormous literature on redox signaling drove research activity towards understanding the role of oxidative stress under normal and challenging conditions like high-altitude hypoxia which grounds for disturbed redox signaling. Excessive ROS production and accumulation of free radicals in cells and tissues can cause various pulmonary, cardiovascular, and metabolic pathophysiological conditions. In order to counteract this oxidative stress and maintain the balance of pro-oxidants and anti-oxidants, an anti-oxidant system exists in the human body, which, however, gets surpassed by elevated ROS levels, but can be strengthened through the use of anti-oxidant supplements. Such cumulative studies of fundamentals on a global concept like oxidative stress and role of anti-oxidants can act as a foundation to further smoothen for researchers to study over health, disease, and other pathophysiological conditions. This review highlights the interconnection between high altitude and oxidative stress and the role of anti-oxidants to protect cells from oxidative damages and to lower the risk of altitude-associated sickness.