Role of leptin as antioxidant in obstructive sleep apnea: an in vitro study using electron paramagnetic resonance method.
BACKGROUND
As in obstructive sleep apnea (OSA), the chronic cycles of hypoxia and reoxygenation are thought to be conducive of oxidative stress (OS) with generation of reactive oxygen species, identifying effective mechanisms of protection against oxidant-mediated tissue damage becomes of outmost importance. Leptin's role had been recently extended into that of participant to OS; while its exact role in this process is yet to be defined, elevated leptin levels correlate significantly with several indices of OSA disease severity such as nocturnal hypoxemia, possibly acting as a counteractive mechanism against the chronic intermittent hypoxia-related OS and serving as a marker of future risk of atherosclerotic disease. We therefore investigated leptin's antioxidant mechanism on superoxide (O (2) (-•) ) anions using spectrophotometry and electron paramagnetic resonance (EPR).


METHODS
The O (2) (-•) was generated by oxidation of xanthine (XAN) by xanthine oxidase (XO) in the presence of spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide with various concentrations of leptin (0.001, 0.01, 0.1, and 1 mg/ml) and without leptin. Signal intensity between 3,440 and 3,540 G was expressed as standard means ± SD. The activity of leptin on XO was determined by monitoring the conversion of XAN to uric acid at 293 nm using a Beckman DU 800 UV-visible spectrophotometer.


RESULTS
Leptin added to aqueous solutions at 0.1 and 1 mg/ml concentrations was associated with a statistically significant decrease in the EPR signal due to leptin's direct scavenging activity towards the O (2) (-•) .


CONCLUSIONS
Leptin is an antioxidant agent of possible use as a marker of OS and future risk of atherosclerotic disease in OSA.
University of Virginia School of Medicine, Charlottesville, VA, USA. Madalina.Macrea@va.gov
Madalina
M
Macrea
Thomas
T
Martin
Leon
L
Zagrean
Zhenquan
Z
Jia
Hara
H
Misra
D000975:Antioxidants / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D066298:In Vitro Techniques; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D020738:Leptin; D017382:Reactive Oxygen Species; D013481:Superoxides