The effects of high-altitude exposure on reactive oxygen and nitrogen species

High-altitude exposure that results in decreased levels of oxygen pressure, which could lead to hypoxia, can activate a number of sources that can generate reactive oxygen and nitrogen species (RONS). Enhanced formation of RONS causes oxidative damage, which impacts cellular function and could seriously impair organ function. In addition, high altitude appears to weaken the enzymatic and nonenzymatic antioxidant systems. Indeed, recent data suggest that the expression of Mn-SOD in skeletal muscle of mountaineers, who stayed for more than 6 weeks above 6,000 m, decreased significantly 1 week after leaving that altitude. Moreover, the expression of Ku70, which plays an important role in DNA repair, increased after exposure to high altitude, indicating increased DNA damage. Therefore, it appears that increased nutritional uptake of antioxidant vitamins reduce altitude-induced oxidative damage. The pattern of high-altitude exposure-associated oxidative damage is similar to ischemia/reperfusion injury. The adaptive process for this oxidative challenge is relatively long, and physical exercise or enhanced levels of physical activity at high altitude exacerbate the extent of the oxidative challenge. Therefore, special attention must be given to any and all processes which modulate the degree of oxidative stress.