Systemic redox homeostasis is minimally perturbed by
extended low pO2 exposure
With our long-term objective being translation to humans, we studied the
plasma proteome after investigating key molecular aspects of the lung
proteome. However, before the proteome based investigation, we performed
a basic biochemical investigation into redox parameters. Oxidative
stress was estimated via ROS, TBARS and NOx levels (Fig. S4 a, b & c,Supplementary information ). ROS and TBARS showed slight increase
in HD3 with HD7 and HD14 tending towards normalized values of both. NOx,
on the other hand, showed its minimal value in HD3 and maximal value in
HD7 while HD14 had levels similar to Normoxia.
We then investigated central antioxidant molecules’ concentration and
activity in plasma (Fig. S4 d, e, f & g, Supplementary
information ). Contrary to our observations in previous study (Paul et
al., 2018), we observe an anti-trend in TAC values in lung (Fig. S1d,Supplementary information ) and plasma (Fig. S4d,Supplementary information ). In HD3, TAC values show a decrease
with sequential increases in both HD7 and HD14. HD14 had TAC value very
similar to Normoxia TAC value. A similar trend is observed in catalase
activity. SOD activity, on the other hand, remains constant across HD7
and HD14 after a slight increase in HD3. Total GSH also tends to remain
constant throughout the low pO2 exposed groups.
A hierarchical clustergram representing expression trends of
redox-specific transcripts in blood of Normoxia, HD3, HD7 and HD14 group
rats (Fig. S5, Supplementary information ) revealed some redox
responsive transcripts to have similar trends across HD3, HD7 and HD14
while some transcripts had similar expression in Normoxia, HD3, HD7 with
opposing trends in Normoxia or HD14, respectively. Thus,
non-directionality of the redox transcript-based assessment suggested
redox stress homeostasis is maintained during extended exposure to low
pO2 8.19 kPa (observed at altitudes of 25,000 ft).