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.