Effects of a vitamin E-modified dialysis membrane on neutrophil superoxide anion radical production

Abstract

Activation of neutrophil by the dialysis membrane and peroxidative stress plays an important role on the pathogenesis of complications in hemodialysis (HD) patients. Vitamin E is one of the potent scavengers for reactive oxygen species. Recent studies suggest that a vitamin E-modified multilayer membrane (Excebrane, CL-EE dialyzer) has an inhibitory effect on serum lipids peroxidation in HD patients. To determine the effect of CL-EE on biocompatibility in clinical use, we measured the superoxide anion radical producing ability (SOPA) of polymorphonuclear leukocytes (PMNLs), the plasma hydroxyl radical producing ability (OHPA) and superoxide anion radical scavenging activity (SSA). SOPA was measured after stimulation of PMNLs with phorbol myristate acetate using electron paramagnetic resonance (EPR) method. Plasma OHPA and SSA were also determined using the EPR method. In addition, the plasma concentrations of malondialdehyde (MDA) and oxidized low-density lipoprotein (LDL), as the parameters for lipid peroxidation, were measured. SOPA was decreased in patients who used conventional filter membrane compared with healthy controls. In the patients using the CL-EE membrane, SOPA gradually increased and reached control levels after six months. However, no significant increase was observed in patients who used a conventional filter membrane. OHPA of HD patients was significantly decreased compared with controls. In the CL-EE membrane patient group, OHPA was significantly increased at six months. SSA was significantly higher in the conventional filter membrane group than controls. In the CL-EE membrane patient group, SSA gradually decreased at six months. Plasma MDA and oxidized LDL levels were significantly higher in HD patients compared with controls. These values slowly decreased, and significant differences were found after nine months of using the CL-EE membrane. These findings suggest that activation of PMNLs and plasma OHPA and SSA in HD patients is attenuated by antioxidant effects of the CL-EE.

Comparative effects of dietary supplementation with red grape juice and vitamin E on production of superoxide by circulating neutrophil NADPH oxidase in hemodialysis patients

“…In hemodialysis patients, coating of the dialyzer membranes with vitamin E has been used to prevent the neutrophil activation otherwise induced by the hemodialysis procedure (9,10). The results of this study confirm and extend these observations to show that administration of vitamin E at a dose of 800 IU every other day causes a significant reduction in NADPH oxidase-mediated superoxide production in neutrophils, as measured by the DHR method.…”

“…The strong positive correlation between apoB and plasma concentrations of oxidized LDL found in the general population (43,50) may reduce the predictive value of oxidized LDL, as measured with monoclonal antibody E46, when lipid-normalized values are introduced in the multivariate model (54). It is noteworthy that the elevated plasma concentrations of oxidized LDL that hemodialysis patients usually have (10,(12)(13)(14)30) cannot be attributed to apoB, because the regression line between apoB and oxidized LDL observed in these patients is well above that in controls (30). Thus, factors other than apoB must explain these differences.…”

“…Furthermore, the hemodialysis procedure itself causes oxidative stress by generating ROS through activation of circulating neutrophils (8,9). Coating dialysis membranes with vitamin E has been shown to effectively reduce superoxide anion production by neutrophils (9,10) and to lower the plasma concentration of oxidized LDL (8,9,11), an emerging marker for cardiovascular risk in hemodialysis patients (12)(13)(14).…”

Mechanisms of H2O2-induced oxidative stress in endothelial cells

“…Vitamin E is lipid soluble, scavenges ROS directly, and may have a role in protecting against LDL oxidation (Fontana et al 1999;Carr et al 2000c;Shimazu et al 2001). …”

Current Studies on Oxidant Stress in Dialysis

“…Miyazaki et al [42] observed that use of the cartridge maintained pre-treatment levels of NO-induced brachial reactivity, and suppressed posttreatment formation of ox-LDL. Shimazu et al [43] found that dialysis with conventional membranes impaired the function of neutrophils, suggesting that the neutrophils had been degranulated and inactivated by passage through the dialyzer; treatment with the vitamin-E dialyzer prevented the impairment. Similar protection of neutrophil function was observed with the vitamin E dialyzer by Omata et al [44].…”