Increased oxidative stress and reduced antioxidant enzyme activity in obstructive sleep apnea syndrome

Sevda İsmailoğulları, Murat Gültekin, Gülden Başkol, Murat Aksu
1.908 662


Background: Obstructive sleep apnea (OSA) is associated with neurological complications. An increase in hypoxia due to OSA may cause generation of reactive oxygen species (ROS) via hypoxia-activated enzyme xanthine oxidase (XO) in the last reactions of the purine catabolism. Another enzyme playing a part in purine metabolism is adenosine deaminase (ADA) which is an important enzyme in the maturation and function of T lymphocytes. ROS produced by XO, can reduce antioxidant paraoxonase-1 (PON1). The objective of this study is to determine the activities of  XO, ADA, and PON1 activities in OSA patients in comparison with those in non-apneic controls. Methods: The plasma activities of XO, ADA, and PON1 were determined in 57 patients with OSA (apnea-hypopnea index [AHI]) ≥ 15) of whom 19 had cardiovascular disease (CVD), and 38 had  OSA but were without CVD and 27 non-apneic controls (AHI ≤ 5). A venous blood sample was obtained early in the morning after the polysomnography night. Results: XO and ADA activity was found to be significantly higher in the OSA group than the control group. PON1 activity was found lower in the OSA group, but this result was not statistically significant. Min O2 saturation had a significant independent relationship with ADA activity; and AHI had a significant independent relationship with PON1 activity after adjustment for confounding factors that are considered to be related to oxidative stress.  Conclusions: These results support the existence of oxidative stress in OSA and OSA should be considered as a systemic disease.

Anahtar kelimeler

Obstructive sleep apnea, xanthine oxidase, adenosine deaminase, paraoxonase-1.

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- Iber C, Ancoli-Israel S, Chesson A, Quan SF: The AASM Manual for the scoring of Sleep and Associated events. Rules, Terminology and Technical Spesifications., 1st ed.: Westchester, Illinois: American Academy of Sleep Medicine, 2007.

- Galanti B, Nardiello S, Russo M, Fiorentino F: Increased lymphocyte adenosine deaminase in typhoid fever. Scand J Infect Dis 1981;13:47-50.

- Abrams B: Long-term sleep apnea as a patogenic factor for cell-mediated autoimmune disease. Med Hypotheses 2005;65:1024-7.

- Grum CM, Ragsdale RA, Ketai LH, Simon RH: Plasma xanthine oxidase activity in patients with adult respiratory distress syndrome. J Crit Care 1987;2:22-6.

- Jessup W, Bedwell S, Dean R: The action of defined oxygen centered free radicals on human low density lipoprotein. Biochem J 1989; 262:707-12.

- Zamarron C, Paz VG, Riveiro A. Obstructive sleep apnea syndrome is a systemic disease. Current evidence. European Journal of Internal Medicine 2008;19:390-398.

- Lavie P, Herer P, Hoffstein V: Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study. BMJ 2000; 320:479-82.

- Gan KN, Smolen A, Eckerson HW, et al: Purification of human serum paraoxonase/arylesterase: evidence for one esterase catayzing both activities. Drug Metab Dispos 1991;19:100-6.

- Giblett ER, Andern J: Adenosine deaminase deficiency in two patient with severely impaired cellular immunity. Lancet 1972;18:1067-9.

- Arroyo M, Soberman JE: Adenosine deaminase in the diagnosis of tuberculous pericardial effusion. Am J Med Sci 2008;335:227-9.

- Ozyurt H, IrmakMK, Akyol O, Sogut S: Caffeic acid phenethyl ester changes the indices of oxidative stress in serum of rats with renal ischaemia-reperfusion injury. Cell Biochem Funct 2001;19:259-63.

- Giusti G: Adenosine deaminase. In Methods of Enzymatic Analysis, berg meyer MV (ed.). Academic Press: New York, 1974;1092-8.

- Eckerson EW, Romson J, Wyte C, et al: The serum paraoxonase polymorphism : Identification of phenotypes by their response to salts. Am J Hum Genet 1983;35:214-27.

- Rechtschaffen, A, Kales, A: A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. US Department of Health, Education &Welfare, Neurological Information Network, Bethesda, MD, 1968.

- Nishino T, Okamoto K, Eger BT, et al: Mammalian xanthine oxidase oxidoreductase – mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 2008;275:3278-89.

- Rozenberg O, Rosenblat M, Coleman R, et al: Paraoxonase (PON1) deficiency is associated with increased macrophage oxidative stress: studies in PON1-knockout mice. Free Rad Biol Med 2003;34:774-84.

- McKelvey TG, Hollwarth ME, Granger DN, et al: Mechanisms of conversion of xanthine dehydrogenase to xanthine oxidase in ischemic rat liver and kidney. Am J Physiol 1988;254:753-60.

- Peker Y, Kraiezi H, Hedner J, et al: An independent association between obstructive sleep apnoea and coronary artery disease. Eur Respir J 1999; 14:179-84.

- Adams A, Harkness RA: Adenosine deaminase activity in thymus and human tissues. Clin Exp Immunol 1976;26:647-9.

- Ayub A, Mackness MI, Arrol S, et al: Serum paraoxonase after myocardial infarction. Arterioscler Thromb Vasc Biol 1999;19:330-5.

- Mackness MI, harty D, Bhatnagar D, et al: Serum paraoxonase activity in familial hypercholesterolaemia and insulin dependent diabetes mellitus. Atherosclerosis 1991;86:193-9.

- Aviram M, Rosenblat M, Bisgaiger CL, et al: Paraoxonase inhibits high-density lipoprotein oxidation and preserves its function: A possible peroxidative role for paraoxonase. J Clin Invest 1998;101:1581-90.

- Prajde N, Weber G: Malignat transformation-linked imbalance: decreased XO activity in hepatomas. FEBS Lett 1975;59:245-9.

- Bükülmez G, Akan T, Ciliv G: Serum adenosine deaminase levels in patients with psoriasis: a prospective case-control study. Eur R Dermatol 2000;10:274-6.

- Sogut S, Kotuk M, Yilmaz HR, et al: In vivo evidence suggesting a role for purine-catabolizing enzymes in the pathogenesis of cisplatin-induced nephrotoxicity in rats and effect of erdosteine against this toxicity. Cell Biochem Funct 2004;22:157-62.

- American Academy of Sleep Medicine Task Force: Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999;22:667-89.

- Chambers DE, Parks DA, Patterson G, et al: Xanthine oxidase as a source of free radical damage in myocardial ischemia. J Biol Cell Cardiol 1985;17:145-52.

- Mathur S, Devaraj S, Jialal I: Accelerated atherosclerosis, dyslipidemia, and oxidative stress in end-stage renal disease. Curr Opin Nephrol Hypertens 2002;11:141-7.

- Lavie L, Vishnevsky A, Lavie P: Evidence for lipid peroxidation in obstructive sleep apnea. Sleep 2004;27:123-8.

- Xia Y, Zweier JL: Substrate control of free radical generation from xanthine oxidase in the post ischemic heart. J Biol Chem 1995;270:18797-803.

- Dean RT, Wilcox I: Possible atherogenic effects of hypoxia during obstructive sleep apnea. Sleep 1993;16:15-21.

- Aviram M, Rosenblat M, Billecke S, et al: Human serum paraoxonase (PON1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med 1999;26:892-904.