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).