Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude.
BACKGROUND
Both tissue hypoxia in vitro, and whole-body hypoxia in vivo, have been found to promote the release of reactive oxygen species (ROS) that are potentially damaging to the cardiovascular system. Antioxidant systems protect against oxidative damage by ROS and may exhibit some degree of responsiveness to oxidative stimuli. Production of urate, a potent soluble antioxidant, is increased in hypoxic conditions. We aimed to determine whether urate is an important antioxidant defense in healthy subjects exposed to hypoxia.


METHODS
We conducted a cohort study of 25 healthy lowland volunteers during acute exposure to high altitude (4 days at 3,600 m, followed by 10 days at 5,200 m) on the Apex high-altitude research expedition to Bolivia. We measured markers of oxidative stress (8-isoprostane F2), serum urate concentration, and total plasma antioxidant activity by two techniques: 2,2'-amino-di-[3-ethylbenzthiazole sulfonate] spectrophotometry (total antioxidant status [TAS]) and enhanced chemiluminescence (ECL).


RESULTS
On ascent, F2-isoprostane levels were significantly elevated compared with those at sea level (p < 0.01). After 1 week at high altitude, plasma antioxidant capacity (AOC) by both TAS and ECL, and serum urate concentration were significantly elevated (each p < 0.01 vs sea level), and F2-isoprostane levels were reduced to values at sea level. There was a highly significant correlation between plasma urate and AOC at this stage (ECL, r(2) = 0.59, p = 0.0001; TAS, r(2) = 0.30, p = 0.0062).


CONCLUSIONS
Our results support the hypothesis that urate may act as a responsive endogenous antioxidant in high-altitude hypoxia.
Baillie
J Kenneth
JK
Apex (Altitude Physiology Expeditions), c/o College of Medicine & Veterinary Medicine, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, UK. j.k.baillie@doctors.org.uk
Bates
Matthew G D
MG
Thompson
A A Roger
AA
Waring
W Stephen
WS
Partridge
Roland W
RW
Schnopp
Martin F
MF
Simpson
Alistair
A
Gulliver-Sloan
Fiona
F
Maxwell
Simon R J
SR
Webb
David J
DJ
D000328:Adult; D000531:Altitude; D000975:Antioxidants / Q000378:metabolism* / Q000502:physiology; D001838:Bolivia; D015331:Cohort Studies; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D008163:Luminescent Measurements; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014527:Uric Acid / Q000097:blood* / Q000378:metabolism
D000975:Antioxidants; D028441:F2-Isoprostanes; D017382:Reactive Oxygen Species; D014527:Uric Acid