Redox homeostasis remained unperturbed past 3rd day of low pO2 exposure
Due to our previous study re-affirming redox stress as the principal component of environmental hypoxia (Paul et al., 2018), we began with a biochemical investigation of the lung to determine redox parameters. ROS (Fig. S1a, Supplementary information ) and TBARS (Fig. S1b,Supplementary information ) levels tend to increase significantly at HD3. In HD7 and HD14, there is near restoration of ROS and TBARS levels to those observed in Normoxia group. NOx levels were also measured. NOx levels were minimally up-regulated across HD3-HD14 relative to Normoxia (Fig. S1c).
As the next logical step, we investigated the antioxidant defenses of the lung during hypoxia exposure. TAC (total antioxidant capacity) was nearly twice in HD3 as compared to Normoxia. However, in HD7 and HD14, TAC levels declined successively but remained higher than Normoxia (Fig. S1d, Supplementary information ). Interestingly, we observed catalase (Fig. S1e, Supplementary information ) and SOD (superoxide dismutase; Fig. S1f, Supplementary information ) activity levels to remain nearly constant throughout Normoxia and HD3-HD14. Total glutathione (GSH) concentrations were observed to successively increase at HD3 and HD7 before declining in HD14 to levels similar to Normoxia (Fig. S1g, Supplementary information ).
We analyzed redox stress specific transcripts in the lung (Fig. S2,Supplementary information ) to further determine the response to chronic environmental hypoxia. The hierarchical clustergram did not provide any clear directionality as to which groups have the overall highest or lowest transcripts’ expression. Almost all transcripts had similar expression across groups. This indicated that redox stress was minimized after the third day of simulated altitude exposure.