Sleep and Breathing

, Volume 16, Issue 2, pp 393–398 | Cite as

Oxidative and carbonyl stress in patients with obstructive sleep apnea treated with continuous positive airway pressure

  • Peter CelecEmail author
  • Július Hodosy
  • Michal Behuliak
  • Roland Pálffy
  • Roman Gardlík
  • Lukáč Halčák
  • Imrich Mucska
Original Article



The pathogenesis of cardiovascular complications of obstructive sleep apnea syndrome (OSAS) can be explained by oxidative and carbonyl stress due to oxygenation and reoxygenation injury during sleep. This hypothesis has yet to be proved experimentally, although several clinical observations have found increased oxidative damage in plasma. Continuous positive airway pressure (CPAP) improves symptoms and prognosis of patients with OSAS.


Patients with confirmed SAS (n = 89) underwent polysomnography and received CPAP treatment. Plasma and saliva samples were taken before CPAP therapy as well as after 1 and 6 months of CPAP treatment. Selected markers of oxidative and carbonyl stress were measured in plasma and saliva, and their dynamics was statistically analyzed.


Plasma levels of thiobarbituric acid reacting substances—a marker of lipoperoxidation—and advanced glycation end products (AGEs)—a marker of carbonyl stress—were decreased by the CPAP therapy. The decrease of AGEs and fructosamine was also found in saliva. Interestingly, no gender differences and no changes of antioxidant status measured as total antioxidant capacity and ferrous reducing ability were found in either of the samples.


Previous findings of lowered plasma markers of oxidative stress were confirmed. Plasma AGEs were lowered by CPAP therapy. This is the first study analyzing markers of oxidative and carbonyl stress in saliva. Non-invasive sampling of saliva makes it a very interesting source of information for repeated monitoring of therapy success. Salivary AGEs and fructosamine as markers of carbonyl stress were decreased by the CPAP therapy and might therefore have potential informative value for clinical observations, as well as for the understanding of the pathogenesis of OSAS complications.


Sleep apnea Advanced glycation Salivary malondialdehyde Oxidative stress Carbonyl stress 



Peter Celec designed the study, performed biochemical analyses, and wrote the manuscript. Michal Behuliak, Roland Pálffy, and Roman Gardlík performed the biochemical analyses. Lukáč Halčák and Július Hodosy managed the study and the analyses. Imrich Mucska contacted the patients and collected samples.

The authors would like to thank all the patients for participating in the study. This study was sponsored by the Slovak Research and Development Agency, grant VMSP-II-0027-09.

Conflict of interest for all authors

None to declare


  1. 1.
    Jurkovicova I, Celec P (2004) Sleep apnea syndrome and its complications. Acta Med Austriaca 31:45–50PubMedGoogle Scholar
  2. 2.
    Lavie L, Lavie P (2009) Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link. Eur Respir J 33:1467–1484PubMedCrossRefGoogle Scholar
  3. 3.
    Miyata T, de Strihou CV, Kurokawa K, Baynes JW (1999) Alterations in nonenzymatic biochemistry in uremia: origin and significance of “carbonyl stress” in long-term uremic complications. Kidney Int 55:389–399PubMedCrossRefGoogle Scholar
  4. 4.
    Streckfus CF, Bigler LR (2002) Saliva as a diagnostic fluid. Oral Dis 8:69–76PubMedCrossRefGoogle Scholar
  5. 5.
    Celec P, Hodosy J, Celecova V, Vodrazka J, Cervenka T, Halcak L, Bozek P, Kopani M, Kudela M (2005) Salivary thiobarbituric acid reacting substances and malondialdehyde—their relationship to reported smoking and to parodontal status described by the papillary bleeding index. Dis Markers 21:133–137PubMedGoogle Scholar
  6. 6.
    Becker HF, Jerrentrup A, Ploch T, Grote L, Penzel T, Sullivan CE, Peter JH (2003) Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 107:68–73PubMedCrossRefGoogle Scholar
  7. 7.
    Kaneko Y, Floras JS, Usui K, Plante J, Tkacova R, Kubo T, Ando S, Bradley TD (2003) Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med 348:1233–1241PubMedCrossRefGoogle Scholar
  8. 8.
    Marin JM, Carrizo SJ, Vicente E, Agusti AGN (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea–hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365:1046–1053PubMedGoogle Scholar
  9. 9.
    Murri M, Alcazar-Ramirez J, Garrido-Sanchez L, Linde F, Alcaide J, Cardona F, Tinahones FJ (2009) Oxidative stress and metabolic changes after continuous positive airway pressure treatment according to previous metabolic disorders in sleep apnea–hypopnea syndrome patients. Transl Res 154:111–121PubMedCrossRefGoogle Scholar
  10. 10.
    Christou K, Kostikas K, Pastaka C, Tanou K, Antoniadou I, Gourgoulianis KI (2009) Nasal continuous positive airway pressure treatment reduces systemic oxidative stress in patients with severe obstructive sleep apnea syndrome. Sleep Med 10:87–94PubMedCrossRefGoogle Scholar
  11. 11.
    Carpagnano GE, Kharitonov SA, Resta O, Foschino-Barbaro MP, Gramiccioni E, Barnes PJ (2003) 8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy. Chest 124:1386–1392PubMedCrossRefGoogle Scholar
  12. 12.
    Moser D, Anderer P, Gruber G, Parapatics S, Loretz E, Boeck M, Kloesch G, Heller E, Schmidt A, Danker-Hopfe H, Saletu B, Zeitlhofer J, Dorffner G (2009) Sleep classification according to AASM and Rechtschaffen & Kales: effects on sleep scoring parameters. Sleep 32:139–149PubMedGoogle Scholar
  13. 13.
    Hodosy J, Celec P (2005) Daytime of sampling, tooth-brushing and ascorbic acid influence salivary thiobarbituric acid reacting substances—a potential clinical marker of gingival status. Dis Markers 21:203–207PubMedGoogle Scholar
  14. 14.
    Ohkawa H, Ohishi N, Yagi K (1978) Reaction of linoleic acid hydroperoxide with thiobarbituric acid. J Lipid Res 19:1053–1057PubMedGoogle Scholar
  15. 15.
    Witko-Sarsat V, Friedlander M, CapeillereBlandin C, NguyenKhoa T, Nguyen NT, Zingraff J, Jungers P, DescampsLatscha B (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 49:1304–1313PubMedCrossRefGoogle Scholar
  16. 16.
    Munch G, Keis R, Wessels A, Riederer P, Bahner U, Heidland A, Niwa T, Lemke HD, Schinzel R (1997) Determination of advanced glycation end products in serum by fluorescence spectroscopy and competitive ELISA. Eur J Clin Chem Clin Biochem 35:669–677PubMedGoogle Scholar
  17. 17.
    San-Gil F, Schier GM, Moses RG, Gan IE (1985) Improved estimation of fructosamine, as a measure of glycated serum protein, with the Technicon RA-1000 analyzer. Clin Chem 31:2005–2006PubMedGoogle Scholar
  18. 18.
    Erel O (2004) A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 37:277–285PubMedCrossRefGoogle Scholar
  19. 19.
    Benzie IFF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76PubMedCrossRefGoogle Scholar
  20. 20.
    Dikmenoglu N, Ciftci B, Ileri E, Guven SF, Seringec N, Aksoy Y, Ercil D (2006) Erythrocyte deformability, plasma viscosity and oxidative status in patients with severe obstructive sleep apnea syndrome. Sleep Med 7:255–261PubMedCrossRefGoogle Scholar
  21. 21.
    Jordan W, Cohrs S, Degner D, Meier A, Rodenbeck A, Mayer G, Pilz J, Ruther E, Kornhuber J, Bleich S (2006) Evaluation of oxidative stress measurements in obstructive sleep apnea syndrome. J Neural Transm 113:239–254PubMedCrossRefGoogle Scholar
  22. 22.
    Selmi C, Montano N, Furlan R, Keen CL, Gershwin ME (2007) Inflammation and oxidative stress in obstructive sleep apnea syndrome. Exp Biol Med 232:1409–1413CrossRefGoogle Scholar
  23. 23.
    Ozkan Y, Firat H, Simsek B, Torun M, Yardim-Akaydin S (2008) Circulating nitric oxide (NO), asymmetric dimethylarginine (ADMA), homocysteine, and oxidative status in obstructive sleep apnea–hypopnea syndrome (OSAHS). Sleep Breath 12:149–154PubMedCrossRefGoogle Scholar
  24. 24.
    Ryan S, Taylor CT, McNicholas WT (2005) Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation 112:2660–2667PubMedCrossRefGoogle Scholar
  25. 25.
    Greenberg H, Ye XB, Wilson D, Htoo AK, Hendersen T, Liu SF (2006) Chronic intermittent hypoxia activates nuclear factor-kappa B in cardiovascular tissues in vivo. Biochem Biophys Res Commun 343:591–596PubMedCrossRefGoogle Scholar
  26. 26.
    Suzuki YJ, Jain V, Park AM, Day RM (2006) Oxidative stress and oxidant signaling in obstructive sleep apnea and associated cardiovascular diseases. Free Radic Biol Med 40:1683–1692PubMedCrossRefGoogle Scholar
  27. 27.
    Yamauchi M, Kimura H (2008) Oxidative stress in obstructive sleep apnea: putative pathways to the cardiovascular complications. Antioxid Redox Signal 10:755–768PubMedCrossRefGoogle Scholar
  28. 28.
    Lykkesfeldt J (2007) Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking. Clin Chim Acta 380:50–58PubMedCrossRefGoogle Scholar
  29. 29.
    WitkoSarsat V, Friedlander M, CapeillereBlandin C, NguyenKhoa T, Nguyen NT, Zingraff J, Jungers P, DescampsLatscha B (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 49:1304–1313CrossRefGoogle Scholar
  30. 30.
    Capeillere-Blandin C, Gausson V, Descamps-Latscha B, Witko-Sarsat V (2004) Biochemical and spectrophotometric significance of advanced oxidized protein products. Biochim Biophys Acta Mol Basis Dis 1689:91–102Google Scholar
  31. 31.
    Hernandez C, Abreu J, Abreu P, Colino R, Jimenez A (2006) Effects of nasal positive airway pressure treatment on oxidative stress in patients with sleep apnea–hypopnea syndrome. Arch Bronconeumol 42:125–129PubMedCrossRefGoogle Scholar
  32. 32.
    Takahashi KI, Chin K, Nakamura H, Morita S, Sumi K, Oga T, Matsumoto H, Niimi A, Fukuhara S, Yodoi J, Mishima M (2008) Plasma thioredoxin, a novel oxidative stress marker, in patients with obstructive sleep apnea before and after nasal continuous positive airway pressure. Antioxid Redox Signal 10:715–726PubMedCrossRefGoogle Scholar
  33. 33.
    Lavie P, Lavie L (2009) Unexpected survival advantage in elderly people with moderate sleep apnoea. J Sleep Res 18:397–403PubMedCrossRefGoogle Scholar
  34. 34.
    Grebe M, Eisele HJ, Weissmann N, Schaefer C, Tillmanns H, Seeger W, Schulz R (2006) Antioxidant vitamin C improves endothelial function in obstructive sleep apnea. Am J Respir Crit Care Med 173:897–901PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Peter Celec
    • 1
    • 2
    • 3
    Email author
  • Július Hodosy
    • 1
    • 4
  • Michal Behuliak
    • 1
    • 2
  • Roland Pálffy
    • 1
    • 2
  • Roman Gardlík
    • 5
  • Lukáč Halčák
    • 6
  • Imrich Mucska
    • 7
  1. 1.Institute of Molecular BiomedicineComenius UniversityBratislavaSlovakia
  2. 2.Institute of PathophysiologyComenius UniversityBratislavaSlovakia
  3. 3.Department of Molecular BiologyComenius UniversityBratislavaSlovakia
  4. 4.Institute of PhysiologyComenius UniversityBratislavaSlovakia
  5. 5.Institute of Molecular BiomedicineComenius UniversityBratislavaSlovakia
  6. 6.Institute of Chemistry, Biochemistry and Clinical BiochemistryComenius UniversityBratislavaSlovakia
  7. 7.Sleep Laboratory, University HospitalComenius UniversityBratislavaSlovakia

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