Increased Oxidative Stress Following Acute and Chronic High Altitude Exposure

Abstract

The generation of reactive oxygen species is typically associated with hyperoxia and ischemia reperfusion. Recent evidence has suggested that increased oxidative stress may occur with hypoxia. We hypothesized that oxidative stress would be increased in subjects exposed to high altitude hypoxia. We studied 28 control subjects living in Lima, Peru (sea level), at baseline and following 48 h exposure to high altitude (4300 m). To assess the effects of chronic altitude exposure, we studied 25 adult males resident in Cerro de Pasco, Peru (altitude 4300 m). We also studied 27 subjects living in Cerro de Pasco who develop excessive erythrocytosis (hematocrit > 65%) and chronic mountain sickness. Acute high altitude exposure led to increased urinary F(2)-isoprostane, 8-iso PGF(2 alpha) (1.31 +/- 0.8 microg/g creatinine versus 2.15 +/- 1.1, p = 0.001) and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.37 +/- 0.09, p = 0.002), with a trend to increased plasma thiobarbituric acid reactive substance (TBARS) (59.7 +/- 36 pmol/mg protein versus 63.8 +/- 27, p = NS). High altitude residents had significantly elevated levels of urinary 8-iso PGF(2 alpha) (1.3 +/- 0.8 microg/g creatinine versus 4.1 +/- 3.4, p = 0.007), plasma TBARS (59.7 +/- 36 pmol/mg protein versus 85 +/- 28, p = 0.008), and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.55 +/- 0.19, p < 0.0001) compared to sea level. High altitude residents with excessive erythrocytosis had higher levels of oxidative stress compared to high altitude residents with normal hematological adaptation. In conclusion, oxidative stress is increased following both acute exposure to high altitude without exercise and with chronic residence at high altitude.

Effects of exercise and training in hypoxia on antioxidant/pro-oxidant balance

“…In contrast, the maximal exercise performed under hypoxia induced a significant increase in plasma MDA ( þ 56%) and AOPP ( þ 44%). Cellular generation of ROS under hypoxia was reported previously in animals at rest (Hitka et al, 2003), and in humans at high altitude (Simon-Schnass, 1996;Jefferson et al, 2004) and in hypobaric chambers (Joanny et al, 2001).…”

“…In resting conditions, oxidative stress markers have been detected in humans under hypobaric hypoxia (Bailey et al, 2001a;Jefferson et al, 2004), at simulated altitude in hypobaric chambers (Joanny et al, 2001) and after breathing gas mixture reduced in O 2 content (Wing et al, 2003). Firstly, the increase in catecholamine production under hypoxic conditions (Mazzeo et al, 1998) could be responsible for oxidative stress.…”

Moderate altitude but not additional endurance training increases markers of oxidative stress in exhaled breath condensate

“…Permanent residence at high altitude was accompanied by increased oxidative stress (Jefferson et al 2004), and one day of high altitude hypoxia in sedentary lowlanders was associated with increased steady-state levels of oxidative DNA damage (Moller et al 2001). However, prolonged hypoxic exposure in lowlanders showed an adaptive response to oxidative stress.…”

Increased isoprostane levels in oleic acid-induced lung injury

“…Indeed, we found that the changes in isoprostanes in plasma and lung lymph were significantly correlated with the severity of hypoxemia 2 hours after oleic acid administrationin the present study. Jefferson et al [23] measured plasma isoprostane concentrations after acute (48 hours) and chronic high altitude exposures in normal subjects and found significantly increased levels of isoprostanes. These findings were consistent with those of another report showing increased levels of plasma thiobarbituric acid reactive substances in normal subjects after exposure to chronic hypoxia [24].…”