Research Article
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The Effects of Hypoxia on Oxidative Stress, Inflammation, and DNA in Patients With Severe Sleep Apnea Syndrome

Year 2018, Volume: 25 Issue: 4, 456 - 461, 01.12.2018
https://doi.org/10.17343/sdutfd.411066

Abstract

Object: Obstructive sleep apnea syndrome is a disease associated with recurrent apnea-hypopneas during sleep. Apnea-hypopnea attacks cause hypoxia by lowering oxygen saturation levels. Oxidative stress induced by hypoxia can lead to inflammation and DNA damage. The aim of this study was to investigate the effects of intermittent hypoxia on oxidative stress, inflammation, and DNA in severe OSAS patients. Methods: A total of 67 individuals were measured by polysomnography during the night. Peripheral ven blood was collected. Cholesterol, triglyceride, HDL, hs-CRP, TAS and TOS values of all subjects were measured in blood serum by calorimetric method. The comet assay method was used to investigate DNA damage. Results: We found a statistically significant increase in oxidative stress and inflammation parameters in severe OSAS patients (p <0.05). Furthermore, we could not detect the effect of severe OSAS disease on DNA damage. (p>0,05). Conclusions: Our results showed that oxidative stress and inflammatory markers changed markedly in severe OSAS patients. However, the absence of DNA damage despite increased oxidative stress has been interpreted as hypoxia, which is not long enough to damage DNA and does not cause DNA damage alone.

References

  • [1] Gaudette E, Kimoff R. 3 Pathophysiology of OSA. European Respiratory Monograph. 2010(50):31.[2] International classification of sleep disorders—third edition (ICSD-3). AASM Resource Library. 2014.[3] Caples SM, Gami AS, Somers VK. Obstructive sleep apnea. Annals of internal medicine. 2005;142(3):187-97.[4] Sharma H, Sharma S. Overview and implications of obstructive sleep apnoea. Indian journal of chest diseases and allied sciences. 2008;50(1):137.[5] Kato M, Roberts-Thomson P, Phillips BG, Haynes WG, Winnicki M, Accurso V, et al. Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation. 2000;102(21):2607-10.[6] Shamsuzzaman AS, Winnicki M, Lanfranchi P, Wolk R, Kara T, Accurso V, et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation. 2002;105(21):2462-4.[7] Büchner NJ, Quack I, Woznowski M, Stähle C, Wenzel U, Rump LC. Microvascular endothelial dysfunction in obstructive sleep apnea is caused by oxidative stress and improved by continuous positive airway pressure therapy. Respiration. 2011;82(5):409-17.[8] Christou K, Markoulis N, Moulas AN, Pastaka C, Gourgoulianis KI. Reactive oxygen metabolites (ROMs) as an index of oxidative stress in obstructive sleep apnea patients. Sleep and Breathing. 2003;7(03):105-10.[9] Møller P, Loft S, Lundby C, Olsen NV. Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans. The FASEB Journal. 2001;15(7):1181-6.[10] Cleland SJ, Sattar N, Petrie JR, Forouhi NG, Elliott HL, Connell JM. Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clinical science. 2000;98(5):531-5.[11] Fichtlscherer S, Rosenberger G, Walter DH, Breuer S, Dimmeler S, Zeiher AM. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation. 2000;102(9):1000-6.[12] Organization WH. Global database on Body Mass Index: BMI Classification. 2006. World Health Organization Retrieved. 2016;16.[13] Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. 2005;38(12):1103-11.[14] Tremblay AJ, Morrissette H, Gagne J-M, Bergeron J, Gagné C, Couture P. Validation of the Friedewald formula for the determination of low-density lipoprotein cholesterol compared with β-quantification in a large population. Clinical biochemistry. 2004;37(9):785-90.[15] Collins AR. The comet assay for DNA damage and repair. Molecular biotechnology. 2004;26(3):249.[16] Collins AR, Ai-Guo M, Duthie SJ. The kinetics of repair of oxidative DNA damage (strand breaks and oxidised pyrimidines) in human cells. Mutation Research/DNA Repair. 1995;336(1):69-77.[17] Ntalapascha M, Makris D, Kyparos A, Tsilioni I, Kostikas K, Gourgoulianis K, et al. Oxidative stress in patients with obstructive sleep apnea syndrome. Sleep and Breathing. 2013;17(2):549-55.[18] Droge W. Free radicals in the physiological control of cell function. Physiological reviews. 2002;82(1):47-95.[19] Jordan W, Reinbacher A, Cohrs S, Grunewald RW, Mayer G, Rüther E, et al. Obstructive sleep apnea: plasma endothelin-1 precursor but not endothelin-1 levels are elevated and decline with nasal continuous positive airway pressure. Peptides. 2005;26(9):1654-60.[20] Kontogianni K, Messini‐Nikolaki N, Christou K, Gourgoulianis K, Tsilimigaki S, Piperakis SM. DNA damage and repair capacity in lymphocytes from obstructive sleep apnea patients. Environmental and molecular mutagenesis. 2007;48(9):722-7.[21] Xie J, Jiang J, Shi K, Zhang T, Zhu T, Chen H, et al. DNA damage in peripheral blood lymphocytes from patients with OSAHS. Sleep and Breathing. 2014;18(4):775-80.[22] Kang IG, Jung JH, Kim ST. The effect of obstructive sleep apnea on DNA damage and oxidative stress. Clinical and experimental otorhinolaryngology. 2013;6(2):68.[23] Önder B, Aç P, Öztura İ, İtil O, Gülcü A, Altekin E , Göktay AY, Sarı İ, Bayraktar F, Yeşil S. C-Reactive protein levels in obstructive sleep apnea patients. DEÜ Tip Fakültesi Dergisi 2012; 26(3): 165 - 72.[24] Kim J, Lee SJ, Choi KM, Lee SK, Yoon DW, Lee SG, et al. Obstructive Sleep Apnea Is Associated with Elevated High Sensitivity C-Reactive Protein Levels Independent of Obesity: Korean Genome and Epidemiology Study. PloS one. 2016;11(9):e0163017.

Ağır Uyku Apne Sendromlu Hastalarda Hipoksinin Oksidatif Stres, İnflamasyon ve DNA Üzerine Etkisi

Year 2018, Volume: 25 Issue: 4, 456 - 461, 01.12.2018
https://doi.org/10.17343/sdutfd.411066

Abstract

Amaç: Obstrüktif uyku apne sendromu, uyku sırasında tekrarlayan apne-hipopne ile ilişkili bir hastalıktır. Apne-hipopne atakları oksijen satürasyon seviyelerini düşürerek hipoksiye neden olur. Hipoksinin neden olduğu oksidatif stres, inflamasyona ve DNA hasarına yol açabilir. Bu çalışmanın amacı şiddetli OSAS hastalarında aralıklı hipoksinin oksidatif stres, inflamasyon ve DNA’ya olan etkilerini araştırmaktır. Gereç ve Yöntem: Gece boyunca toplam 67 birey polisomnografi ile ölçüldü. Periferik ven kanı toplandı. Kan serumunda kolesterol, trigliserit, HDL, hs-CRP, TAS ve TOS değerleri kalorimetrik yöntemle ölçüldü. DNA hasarını araştırmak için Comet assay analizi yöntemi kullanıldı. Bulgular: Ağır OSAS hastalarında oksidatif stres ve inflamasyon parametrelerinde istatistiksel olarak anlamlı bir artış saptadık (p <0.05). Bunun yanında, şiddetli OSAS hastalığının DNA hasarı üzerindeki etkisini tespit edemedik. (p> 0.05). Sonuç: Ağır OSAS hastalarında oksidatif stres ve inflamatuar belirteçlerin belirgin olarak arttığını gösterdi. Bununla birlikte, artan oksidatif strese rağmen DNA hasarının olmayışı oluşan hipoksinin DNA’ya hasar verecek kadar uzun süreli olmadığı ve tek başına DNA hasarı oluşturmadığı şeklinde yorumlanmıştır.

References

  • [1] Gaudette E, Kimoff R. 3 Pathophysiology of OSA. European Respiratory Monograph. 2010(50):31.[2] International classification of sleep disorders—third edition (ICSD-3). AASM Resource Library. 2014.[3] Caples SM, Gami AS, Somers VK. Obstructive sleep apnea. Annals of internal medicine. 2005;142(3):187-97.[4] Sharma H, Sharma S. Overview and implications of obstructive sleep apnoea. Indian journal of chest diseases and allied sciences. 2008;50(1):137.[5] Kato M, Roberts-Thomson P, Phillips BG, Haynes WG, Winnicki M, Accurso V, et al. Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation. 2000;102(21):2607-10.[6] Shamsuzzaman AS, Winnicki M, Lanfranchi P, Wolk R, Kara T, Accurso V, et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation. 2002;105(21):2462-4.[7] Büchner NJ, Quack I, Woznowski M, Stähle C, Wenzel U, Rump LC. Microvascular endothelial dysfunction in obstructive sleep apnea is caused by oxidative stress and improved by continuous positive airway pressure therapy. Respiration. 2011;82(5):409-17.[8] Christou K, Markoulis N, Moulas AN, Pastaka C, Gourgoulianis KI. Reactive oxygen metabolites (ROMs) as an index of oxidative stress in obstructive sleep apnea patients. Sleep and Breathing. 2003;7(03):105-10.[9] Møller P, Loft S, Lundby C, Olsen NV. Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans. The FASEB Journal. 2001;15(7):1181-6.[10] Cleland SJ, Sattar N, Petrie JR, Forouhi NG, Elliott HL, Connell JM. Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clinical science. 2000;98(5):531-5.[11] Fichtlscherer S, Rosenberger G, Walter DH, Breuer S, Dimmeler S, Zeiher AM. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation. 2000;102(9):1000-6.[12] Organization WH. Global database on Body Mass Index: BMI Classification. 2006. World Health Organization Retrieved. 2016;16.[13] Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. 2005;38(12):1103-11.[14] Tremblay AJ, Morrissette H, Gagne J-M, Bergeron J, Gagné C, Couture P. Validation of the Friedewald formula for the determination of low-density lipoprotein cholesterol compared with β-quantification in a large population. Clinical biochemistry. 2004;37(9):785-90.[15] Collins AR. The comet assay for DNA damage and repair. Molecular biotechnology. 2004;26(3):249.[16] Collins AR, Ai-Guo M, Duthie SJ. The kinetics of repair of oxidative DNA damage (strand breaks and oxidised pyrimidines) in human cells. Mutation Research/DNA Repair. 1995;336(1):69-77.[17] Ntalapascha M, Makris D, Kyparos A, Tsilioni I, Kostikas K, Gourgoulianis K, et al. Oxidative stress in patients with obstructive sleep apnea syndrome. Sleep and Breathing. 2013;17(2):549-55.[18] Droge W. Free radicals in the physiological control of cell function. Physiological reviews. 2002;82(1):47-95.[19] Jordan W, Reinbacher A, Cohrs S, Grunewald RW, Mayer G, Rüther E, et al. Obstructive sleep apnea: plasma endothelin-1 precursor but not endothelin-1 levels are elevated and decline with nasal continuous positive airway pressure. Peptides. 2005;26(9):1654-60.[20] Kontogianni K, Messini‐Nikolaki N, Christou K, Gourgoulianis K, Tsilimigaki S, Piperakis SM. DNA damage and repair capacity in lymphocytes from obstructive sleep apnea patients. Environmental and molecular mutagenesis. 2007;48(9):722-7.[21] Xie J, Jiang J, Shi K, Zhang T, Zhu T, Chen H, et al. DNA damage in peripheral blood lymphocytes from patients with OSAHS. Sleep and Breathing. 2014;18(4):775-80.[22] Kang IG, Jung JH, Kim ST. The effect of obstructive sleep apnea on DNA damage and oxidative stress. Clinical and experimental otorhinolaryngology. 2013;6(2):68.[23] Önder B, Aç P, Öztura İ, İtil O, Gülcü A, Altekin E , Göktay AY, Sarı İ, Bayraktar F, Yeşil S. C-Reactive protein levels in obstructive sleep apnea patients. DEÜ Tip Fakültesi Dergisi 2012; 26(3): 165 - 72.[24] Kim J, Lee SJ, Choi KM, Lee SK, Yoon DW, Lee SG, et al. Obstructive Sleep Apnea Is Associated with Elevated High Sensitivity C-Reactive Protein Levels Independent of Obesity: Korean Genome and Epidemiology Study. PloS one. 2016;11(9):e0163017.
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Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Articles
Authors

Muhammet Yusuf Tepebaşı

Nilüfer Şahin Calapoğlu

Okan Sancer This is me

Önder Öztürk

Taner Gonca This is me

Halil İbrahim Büyükbayram This is me

Publication Date December 1, 2018
Submission Date March 30, 2018
Acceptance Date July 5, 2018
Published in Issue Year 2018 Volume: 25 Issue: 4

Cite

Vancouver Tepebaşı MY, Şahin Calapoğlu N, Sancer O, Öztürk Ö, Gonca T, Büyükbayram Hİ. The Effects of Hypoxia on Oxidative Stress, Inflammation, and DNA in Patients With Severe Sleep Apnea Syndrome. Med J SDU. 2018;25(4):456-61.

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