Oxidative stress and serum paraoxonase activity in patients on maintenance hemodialysis

摘要

Incidence of atherosclerosis is high in hemodialysis (HD) patients. Paraoxonase may have protective effects against atherosclerosis as it prevents oxidative modification of LDL. Hence, the aim of the present study was to assess the lipid peroxidation and the antioxidant status including paraoxonase activity in HD patients. Thirty HD patients and thirty controls were included in the study. Serum malondialdehyde (MDA) was assessed as a marker of oxidative stress, while antioxidant status was assessed in terms of whole blood reduced glutathione, erythrocyte catalase and serum paraoxonase activity. A statistically significant (p < 0.001) rise of 196 % in serum MDA levels and decline of 36% in erythrocyte catalase activity was noted in HD patients as compared to controls. However, reduced glutathione (GSH) level in whole blood was not altered. Both basal and salt stimulated serum paraoxonase activities were reduced significantly (p < 0.001) as compared to controls with percentage decline of 53% and 37% in basal and salt stimulated paraoxonase activities respectively. These findings indicate that in addition to increased oxidative stress, reduced serum paraoxonase activity could also contribute to development of atherosclerosis in HD through increased oxidative modification of LDL. Introduction Chronic renal failure (CRF) patients have high prevalence of atherosclerotic cardiovascular complications. This is true for patients who are not yet on hemodialysis (HD) and remains so after the initiation of maintenance hemodialysis (1). A tendency to atherosclerosis in these patients may be due to the enhanced oxidative stress resulting from an imbalance between free radicals formation and antioxidant defense mechanism. It has been suggested that oxidative stress is one of the most important “non-conventional” risk factors for atherosclerotic cardiovascular disease (2). According to “oxidative theory” of atherosclerosis, oxidative modification of lipoproteins is considered a key pathological step, with low density lipoprotein (LDL) oxidation being an early event in the development of atherosclerosis. Oxidized LDL (ox-LDL), which is formed as a result of oxidative stress, is taken up by the scavenger receptors of macrophages leading to foam-cell formation. In addition to its pivotal role in foam-cell formation, oxidized-LDL possesses additional atherogenic properties, which include cytotoxicity and the stimulation of thrombotic and inflammatory events (3). High density lipoprotein has a protective effect against atherosclerosis. This effect is due not only to the reverse cholesterol transport activity but is also partly enzymatic. Paraoxonase, a serum esterase – synthesized and secreted by the liver and associated with specific high density lipoprotein (HDL) particle, might be involved in the mechanism (4). Paraoxonase possesses peroxidase like activity that can contribute to protective effect of paraoxonase against LDL oxidation (5). In view of these assumptions, the present study aimed to investigate, in HD patients, the level of oxidative stress and the enzymatic antioxidant status including paraoxonase, an enzyme that prevents oxidative modification of LDL. Materials and methods Thirty CRF patients (16 males and 14 females) on maintenance HD and thirty age matched healthy controls (18 males and 12 females) were included in the study after informed consent had been obtained. Patients with diabetes, inflammatory or malignant diseases were excluded. Primary renal diseases included chronic glomerulonephritis (n = 20), nephroangiosclerosis (n = 4) and chronic interstitial nephritis (n = 6).The mean ages of patient and control groups were 40.56 ± 14.38 years and 43.33 ± 10.8 years respectively. All (CRF) patients included in the study were receiving regular bicarbonate hemodialysis therapy (2-3 hours three times weekly) using high-flux polysulphone hollow fiber dialysers for 2 to 3 years. None of the patients was receiving any antioxidant ther