Leptin's activity on the hydroxyl radical: a possible link to the oxidative stress-related endothelial vasodilation in patients with obstructive sleep apnea

Lung. 2013 Aug;191(4):391-5. doi: 10.1007/s00408-013-9466-4. Epub 2013 May 21.

Abstract

Purpose: Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity, whereas the underlying mechanism is still eluding, the thought participants are chronic intermittent hypoxia with consequent increase in the reactive oxygen species, leading to endothelial cell damage and dysfunction in these patients. As the hydroxyl radical (·OH) mediates the vascular smooth muscle relaxation, identification of its scavengers might reveal sentinel markers of decreased vascular responsiveness and worse long-term comorbid outcome. We therefore assessed leptin's scavenger effect on (∙)OH using the electronic paramagnetic resonance (EPR) method.

Methods: The (∙)OH was generated by the Fenton reaction in the presence of spin-trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DMPO) with various concentrations of leptin (0.25, 2.5, and 25 μg/ml) and without leptin. EPR spectrometer settings were: modulation frequency, 100 kHz; X band microwave frequency, 9.5 GHz; microwave power, 20 mW (milliwatts); modulation amplitude, 1.0 G (gauss); time constant, 160 s; scan time, 200 s; and receiver gain, 1 × l0(5). EPR signal intensity between 3,440 and 3,540 G of measurements taken in at least three separate experiments was reported. Mannitol, a known (∙)OH scavenger, at 100 mM significantly decreased the DMPO-OH adduct formation and was used as the active-control agent.

Results: Leptin added to aqueous solutions at all concentrations was associated with a statistically significant decrease in EPR signal compared with controls due to its scavenging activity towards the ·OH.

Conclusions: Leptin could be further investigated as a sentinel biomarker of decreased vascular responsiveness and future risk of atherosclerotic disease in obese OSA patients.

MeSH terms

  • Electron Spin Resonance Spectroscopy
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiopathology
  • Free Radical Scavengers / chemistry*
  • Free Radical Scavengers / metabolism
  • Humans
  • Hydroxyl Radical / chemistry*
  • Hydroxyl Radical / metabolism
  • Leptin / chemistry*
  • Leptin / metabolism
  • Mannitol / chemistry
  • Oxidative Stress*
  • Sleep Apnea, Obstructive / metabolism*
  • Sleep Apnea, Obstructive / physiopathology
  • Vasodilation*

Substances

  • Free Radical Scavengers
  • Leptin
  • Hydroxyl Radical
  • Mannitol