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Role of leptin as antioxidant in obstructive sleep apnea: an in vitro study using electron paramagnetic resonance method

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Abstract

Introduction

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 .

Conclusion

Leptin is an antioxidant agent of possible use as a marker of OS and future risk of atherosclerotic disease in OSA.

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Abbreviations

ROS:

Reactive oxygen species

O −•2 :

Superoxide anion radical

XO:

Xanthine oxidase

OSA:

Obstructive sleep apnea

SOD:

Superoxide dismutase

VEGF:

Vascular endothelial growth factor

EPR:

Electron paramagnetic resonance

XAN:

Xanthine

DEPMPO:

5-Diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide

PBS:

Phosphate buffered saline

SOD:

Superoxide dismutase

GSH-P:

Glutathione peroxidase

GSH-R:

Glutathione reductase

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Authors and Affiliations

  1. Salem VA Medical Center, affiliate of the University of Virginia School of Medicine, Charlottesville, VA, USA

    Madalina Macrea & Thomas Martin

  2. Physiology Department, “Carol Davila” School of Medicine, Bucharest, Romania

    Leon Zagrean

  3. Department of Biology, University of North Carolina at Greensboro, Greensboro, NC, 27410, USA

    Zhenquan Jia

  4. Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research, Blacksburg, VA, USA

    Hara Misra

  5. Pulmonary Department, Salem VA Medical Center, 1970, Roanoke Blvd, Salem, VA, 24153, USA

    Madalina Macrea

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  1. Madalina Macrea
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Correspondence to Madalina Macrea.

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Macrea, M., Martin, T., Zagrean, L. et al. Role of leptin as antioxidant in obstructive sleep apnea: an in vitro study using electron paramagnetic resonance method. Sleep Breath 17, 105–110 (2013). https://doi.org/10.1007/s11325-012-0656-8

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  • DOI: https://doi.org/10.1007/s11325-012-0656-8

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