Lipid peroxidation and osmotic fragility of red blood cells in sleep-apnea patients

doi:10.1016/S0009-8981(03)00126-8

Clinica Chimica Acta

Volume 332, Issues 1–2, June 2003, Pages 83-88

https://doi.org/10.1016/S0009-8981(03)00126-8 Get rights and content

Abstract

Background: Obstructive sleep apnea (OSA) refers to the occurrence of episodes of complete or partial pharyngeal obstruction with oxyhemoglobin desaturation during sleep. These hypoxia/reoxygenation episodes may cause generation of reactive oxygen species. Reactive oxygen species are toxic to biomembranes and may lead to the peroxidation of lipids. We tested the hypothesis that obstructive sleep apnea is linked to increased oxidative stress and lipid peroxidation. In order to identify target tissue/cell damage, we studied the osmotic fragility of red blood cells. Methods: Six subjects polysomnographically diagnosed as obstructive sleep apnea syndrome and 10 controls were included. After all subjects gave written informed consent, blood samples were collected in the morning between 08:00 and 09:00 a.m. following polysomnography. Blood samples were immediately transferred to the laboratory. Glutathione, lipid peroxidation and osmotic fragility of red blood cells were measured manually. Results: Mean glutathione and lipid peroxidation concentrations of patients were not different than those of control subjects (105.6±38.6 U/g Hb and 3.1±2.3 nmol MDA/l vs. 100.6±62.1 U/g Hb and 3.2±2.8 nmol MDA/l, respectively). In both groups, osmotic fragility of red blood cells was not changed. Conclusion: The present study failed to support the hypothesis that obstructive sleep apnea is linked with increased oxidative stress and lipid peroxidation.

Introduction

Obstructive sleep apnea (OSA) refers to the occurrence of episodes of complete or partial pharyngeal obstruction during sleep. It is characterized by cyclical alterations of arterial oxygen concentration with oxyhemoglobin desaturation developing in response to apneas followed by resumption of oxygen saturation during hyperventilation [1]. These hypoxia/reoxygenation episodes, which may, to some extent, be compared with ischemia/reperfusion [2], may cause an imbalance between reactive oxygen species and the antioxidant reserve that is important for detoxification of these molecules.

Reactive oxygen species are generated as by-products of oxidative metabolism particularly in mitochondria of aerobic cells as well as in red blood cells (RBC) concomitant to spontaneous oxidation of hemoglobin to methemoglobin [3]. Oxygen free radicals are highly reactive and may cause cell and tissue damage by interacting with cell membranes and organelles. Extensive lipid peroxidation in biological membranes causes loss of fluidity, decrease in membrane potential, increased permeability to ions and eventual rupture leading to release of cell and organelle contents [4]. Red blood cell membrane is also prone to lipid peroxidation owing to its high content of polyunsaturated lipids [5] and it has been extensively used to investigate the role of oxidative membrane damage in various pathological conditions [6], [7]. Abnormal susceptibility of RBC lipids to peroxidation is known to reflect similar abnormalities in other organs and tissues [6].

Recent studies accumulated evidence against or in support of increased oxidative stress within the vascular system of patients with OSA. Schulz et al. [2] have shown that the release of free radicals from circulating neutrophils is markedly enhanced in OSA patients. Increased superoxide radical generation, which might have a major impact on the development of cardiovascular disorders, was fully reversed by effective continuous positive airway pressure therapy. Wali et al. [8] failed to find any difference in low-density lipoprotein (LDL) peroxidation and antioxidant enzyme activities between OSA and control subjects. However, data referring to existence and consequences of lipid peroxidation under apneic conditions are not abundant, and thus it is not very clear which enzymes, metabolites and tissues are more sensitive to oxidative stress and hence lipid peroxidation. In this study, we tested the hypothesis that obstructive sleep apnea is linked to increased oxidative stress and lipid peroxidation. We also studied osmotic fragility of RBCs in an attempt to identify target tissue/cell damage.

Section snippets

Subjects

Sixteen non-smoking patients (52±11 years) with suspected sleep apnea were participated in the study. Six subjects were diagnosed as obstructive sleep apnea syndrome. The remaining 10 subjects without sleep apnea served as controls. The study was approved by the local Ethics Committee and written informed consent was signed by the patients before recruitment. All participants underwent venous blood sampling between 08:00 and 09:00 a.m. after an overnight fast following the polysomnographic

Results

There were no significant differences between the patients who met the criteria for obstructive sleep apnea and those who did not with respect to demographic characteristics and body mass index (Table 1). None of the patients were on medications and/or taking alcohol or vitamin supplements. Among patients with obstructive sleep apnea, the mean apnea–hypopnea index was 37±16 episodes/h. Eventually these patients had arterial oxyhemoglobin desaturation and a high number of arousals from sleep

Discussion

The prevalance of cardiovascular disease is increased in OSA [13]. It is thought that this association may be the cause of increased mortality seen in untreated OSA patients [1]. On the other hand, considerable data suggest that LDL oxidation triggers a number of events that can promote both the establishment and progression of atherosclerosis [14] which is a hallmark of cardiovascular disease. Thus, interest in the effects of lipid peroxidation is both clinically relevant to discerning the

References (26)

A. Seven et al.
Antioxidant status in experimental hyperthyroidism: effect of vitamin E supplementation
Clin. Chim. Acta
(1996)
A. Kılınç et al.
Increased erythrocyte susceptibility to lipid peroxidation in human Parkinson's disease
Neurosci. Lett.
(1988)
M. Partinen et al.
Daytime sleepiness and vascular morbidity at seven-year follow-up in obstructive sleep apnea patients
Chest
(1990)
L. Shen et al.
OxLDL induces macrophage γ-GCS_HS protein expression: a role for oxLDL-associated lipid hydroperoxide in GSH synthesis
J. Lipid Res.
(2001)
B. Kalyanaraman et al.
Detection of thiyl radical adducts formed during hydroxyl radical and peroxynitrite-mediated oxidation of thiols—a high resolution ESR spin-trapping study at Q-band (35 GHz)
Anal. Biochem.
(1996)
N. Yan et al.
Amino acid sequence of rat kidney gamma-glutamylcysteine synthetase
J. Biol. Chem.
(1990)
T.T. Rohn et al.
U-101033E (2,4-diamino pyrrolopyrimidine), a potent inhibitor of membrane lipid peroxidation as assessed by the production of 4-hydroxynonenal, malodialdehyde, and 4-hydroxynonenal protein adducts
Biochem. Pharmacol.
(1998)
L.M. Snyder et al.
The role of membrane protein sulphhydryl groups in hydrogen peroxide-mediated membrane damage in human erythrocytes
Biochim. Biophys. Acta
(1988)
K.P. Strohl et al.
Recognition of obstructive sleep apnea
Am. J. Respir. Crit. Care Med.
(1996)
R. Schulz et al.
Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea
Am. J. Respir. Crit. Care Med.
(2000)

J.M.C. Gutteridge

Lipid peroxidation and antioxidants as biomarkers of tissue damage

Clin. Chem.

(1995)

A.S. Yalçın et al.

Cumene hydroperoxide induced in vitro peroxidative changes in human red blood cell membranes

Biochem. Arch.

(1989)

K. Toker et al.

Effect of chronic halothane exposure on lipid peroxidation, osmotic fragility and morphology of rat erythrocytes

J. Appl. Toxicol.

(1990)

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: This study was presented at the 16th Congress of the European Sleep Research Society held in Reykjavic, Iceland, 3–7 June 2002, and published in abstract form in Journal of Sleep Research 2002; 11 (Suppl. 1): 167.

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Lipid peroxidation and osmotic fragility of red blood cells in sleep-apnea patients

Abstract

Introduction

Section snippets

Subjects

Results

Discussion

Clin. Chim. Acta

Neurosci. Lett.

Chest

J. Lipid Res.

Anal. Biochem.

J. Biol. Chem.

Biochem. Pharmacol.

Biochim. Biophys. Acta

Recognition of obstructive sleep apnea

Am. J. Respir. Crit. Care Med.

Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea