Effects of Prolonged Exposure to Hypobaric Hypoxia on Oxidative Stress: Overwintering in Antarctic Concordia Station

Abstract

Concordia Station is the permanent, research station on the Antarctic Plateau at 3230 m. During the eleventh winter-over campaign (DC11-2015; February 2015 to November 2015) at Antarctic Concordia Station, 13 healthy team members were studied and blood samples were collected at six different time points: baseline measurements (T0), performed at sea level before the departure, and during the campaign at 3, 7, 20, 90, and 300 days after arrival at Concordia Station. Reducing the partial pressure of O₂ as barometric pressure falls, hypobaric hypoxia (HH) triggers several physiological adaptations. Among the others, increased oxidative stress and enhanced generation of reactive oxygen/nitrogen species (ROS/RNS), resulting in severe oxidative damage, were observed, which can share potential physiopathological mechanisms associated with many diseases. This study characterized the extent and time-course changes after acute and chronic HH exposure, elucidating possible fundamental mechanisms of adaptation. ROS, oxidative stress biomarkers, nitric oxide, and proinflammatory cytokines significantly increased (range 24-135%) during acute and chronic hypoxia exposure (peak 20^th day) with a decrease in antioxidant capacity (peak 90^th day: -52%). Results suggest that the adaptive response of oxidative stress balance to HH requires a relatively long time, more than 300^th days, as all the observed variables do not return to the preexposition level. These findings may also be relevant to patients in whom oxygen availability is limited through disease (i.e., chronic heart and lung and/or kidney disease) and/or during long-duration space missions.

Figure 1

Experimental protocol and unbalance of ROS and TAC in acute and chronic hypobaric hypoxia. (a) Experimental timeline of the protocol adopted to monitor the acclimation effects during the winter-over campaign (DC11-2015) at Antarctic Concordia Station (637 hPa) on oxidative stress, aminothiol redox, inflammation status, NO metabolism, and Hb spectra. Monitored periods of study session from T0 (baseline) to Tend (300 days) are indicated. (b and d, respectively) The time course of ROS production rate (μmol·min⁻¹) and total antioxidant capacity (TAC) (mM) determined by EPR. (c) The stacked plots of the ROS EPR spectra recorded at baseline (T0), the 90^th day (T4), and the end (Tend) of sojourn at Concordia Station. (e) The stacked plots of the TAC EPR spectra recorded every time: from T0 to Tend.

Figure 2

Acute and chronic hypobaric hypoxia-induced unbalance of oxidative stress and changes in nitric oxide metabolism: (a) thiobarbituric acid-reactive substances (TBARS) (μM); (b) protein carbonyls (PC) (nmol·mg⁻¹ protein); (c) 8-hydroxy-2-deoxyguanosine (8-OH-dG) (ng·mL⁻¹); (d) nitric oxide metabolites (NOx) (μM); (e) inducible nitric oxide synthase (iNOS) (I.U.), time course of concentration data. Data are shown as mean ± SD. Significant differences compared to T0 (baseline): p < 0.05 (∗ symbol).

Figure 3

Inflammatory cytokines during acute and chronic HH. Time course of the IL-6, IL-1β, and IL-10 (pg·mL⁻¹) in plasma. Data are shown as mean ± SD. Significant differences compared to T0 (baseline): p < 0.001 (§ symbol), p < 0.05 (∗ symbol).

Figure 4

Difference Hb spectra. Representative absorption difference spectra (Δ absorbance) obtained from the data of spectra recorded every time subtracting the spectrum recorded at T0. The ocra yellow line: T1, light grey: T2, dark grey: T3, dark blue: T4, and black: Tend. p < 0.01 (# symbol), p < 0.001 (§ symbol), and p < 0.0001 (¶ symbol).