Studies on the relationship between serum albumin concentration and lipid peroxidation in the erythrocyte membrane of maintenance hemodialysis patients

We conducted a study on the long-term prognosis of maintenance hemodialysis patients with and without diabetes mellitus(144 cases). As a result, significant differences were observed in the long-term prognosis over a 15-year period between those with a serum albumin concentration of more than 3.8 g/dl and those with a serum albumin concentration of less than 3.8 g/dl. The group with a serum albumin concentration of more than 3.8 g/dl showed a better prognosis than the group with a concentration of less than 3.8 g/dl. We investigated the levels of thiobarbituric acid-reactive substances (TBA-RS) in the erythrocyte membrane of maintenance hemodialysis patients(23 cases), pre-dialysis uremic phase patients(12 cases) and healthy controls(7 cases). TBA-RS in the erythrocyte membrane of pre-dialysis uremic phase patients was higher than that observed in the other groups. The TBA-RS in the erythrocyte membrane in the maintenance hemodialysis without diabetes mellitus group was lower than that in the pre-dialysis uremic phase group. The TBA-RS in the erythrocyte membrane in the maintenance hemodialysis without diabetes mellitus group thus indicated an inverse relationship with the serum albumin concentration, Kt/V and erythrocyte tocopherol contents. These results suggested that serum albumin protects against erythrocyte membrane lipid peroxidation, and that this function is related to hemodialysis. We thus conclude that hypoalbuminemia appears to increase the oxidative damage and acceleration of arteriosclerosis, while it also worsens the long-term prognosis of maintenance hemodialysis patients.     

Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.     

Red blood cell lipid peroxidation in predialysis chronic renal failure

In hemodialysis patients the pentose-phosphate shunt activity is deficient. As a consequence, the lipid peroxidation of the erythrocyte membranes is increased as shown by the increase in malonyldialdehyde concentrations and is accompanied by a decrease of the level of vitamin E in RBC. In the present study we have found that increased lipid peroxidation of the erythrocyte membranes is present also in chronic renal failure patients in the predialysis state, provided that the serum creatinine levels are higher than 5 mg/dl.     

Alpha and gamma tocopherol metabolism in healthy subjects and patients with end-stage renal disease

BACKGROUND: The metabolism of alpha and gamma tocopherol, the major components of vitamin E, have not been studied in uremic patients. The major pathway of tocopherol metabolism is via phytyl side chain oxidation, leaving carboxyethyl-hydroxychromans (CEHC) as metabolites. Alpha and gamma CEHC are water soluble, renally excreted, with known potent anti-inflammatory and antioxidative properties. METHODS: We examined serum alpha and gamma tocopherol and respective CEHC concentrations in 15 healthy subjects and 15 chronic hemodialysis patients. RESULTS: Serum alpha tocopherol levels were similar in hemodialysis patients (12.03 +/- 1.34 microg/mL) and healthy subjects (11.21 +/- 0.20 microg/mL), while serum gamma tocopherol levels were significantly greater in hemodialysis patients (3.17 +/- 0.37 microg/mL) compared to healthy subjects (1.08 +/- 0.06 microg/mL, P < 0.0001). Serum alpha and gamma CEHC levels were tenfold and sixfold higher in hemodialysis patients compared to healthy subjects, respectively (both P < 0.0001). Serum alpha and gamma tocopherol levels and CEHC metabolites were also measured after supplementation of alpha- or gamma-enriched mixed tocopherols in both hemodialysis patients and healthy subjects. Tocopherol administration resulted in modest or nonsignificant changes in serum tocopherol concentrations, while markedly increasing serum CEHC concentrations in both healthy subjects and hemodialysis patients. Hemodialysis resulted in no change in the serum alpha or gamma tocopherol concentrations while decreasing serum alpha CEHC and gamma CEHC levels by 63% and 53%, respectively (both P = 0.001 versus predialysis). Fourteen-day administration of gamma-enriched but not alpha tocopherols lowered median C-reactive protein (CRP) significantly in hemodialysis patients (4.4 to 2.1 mg/L, P < 0.02). CONCLUSION: First, serum alpha and gamma CEHC accumulate in uremic patients compared to healthy subjects; second, supplementation with tocopherols dramatically increases serum CEHC levels in both healthy subjects and hemodialysis patients; and, finally, CEHC accumulation may mediate anti-inflammatory and antioxidative effects of tocopherols in hemodialysis patients.     

Relationship Between Red Blood Cell Lipid Peroxidation, Plasma Hemoglobin, and Red Blood Cell Osmotic Resistance Before and After Vitamin E Supplementation in Hemodialysis Patients

It has been reported that increased peroxidation of the polyunsaturated fatty acids in the erythrocyte membranes is one of the causes of chronic hemolysis in uremic patients on hemodialysis and that therapeutic doses of vitamin E are effective in reducing peroxidation, improving the hematocrit. The present study shows how the reduced peroxidation, induced by a course with therapeutic doses of vitamin E, is paralleled by a significant reduction of plasma hemoglobin concentrations at the end of the dialysis and by a significant improvement of erythrocyte osmotic resistance. The findings lead to the suggestion that the administration of tocopherol to patients on chronic hemodialysis for end-stage renal disease may be beneficial in improving anemia, acting via a reduction of lipid peroxidation of the red blood cell membranes. Whether this can reduce the need for the transfusions can be assessed only with a longitudinal long-term study, which is also necessary to determine whether the preliminary findings of this report have important clinical applications.     

人心肌缺血／再灌注期间冠状窦血中红细胞流变性的改变

对１５例房或室间隔缺损病人在行体外循环心内直视修补术中，心肌缺血／再灌注期间的冠状静脉窦血中自由基水平、脂质过氧化物、自由基清除酶活性、红细胞变形性和红细胞膜脂质分子及蛋白分子流动性等指标进行了动态观察。结果发现，再灌注后的自由基和脂质过氧化物水平明显增高、血浆ＳＯＤ活性降低及红细胞谷胱苷肽酶活性提高，同时，红细胞膜分子尤其是脂质分子流动性下降，从而导致整个红细胞变形性恶化，这是造成再灌注后微循环障碍的危险因素。     

Evaluation of lipids peroxidation products vs. proinflammatory cytokines in hemodialized patients.

BACKGROUND: Patients with end-stage renal failure on chronic hemodialysis often demonstrate accelerated development of atherosclerotic changes and cardiovascular complications. In those patients oxidative stress facilitates the intensity of lipid peroxidation process, expressed as increased products of lipid peroxidation (malonaldehyde and 4-hydroxyalkenals). Simultaneously, structures modified by peroxidation and glycation of autoantigenic character are formed. Additionally, increase in proinflammatory cytokines is found in their patients on hemodialysis. The aim of the study was to find out the relations between the products of lipid peroxidation and proinflammatory cytokines in patients on hemodialysis. METHODS: Plasma concentrations of malonaldehyde and 4-hydroxyalkenals were estimated by spectrophotometric method, glutathione peroxidase as well as concentration of IL-6, its soluble receptor and TNFalpha were measured using ELISA kits. RESULTS: Aldehyde concentrations (malonaldehyde and 4-hydroxyalkenals) were found to be five fold higher in comparison with the controls. Concentrations of proinflammatory cytokines: IL-6, TNFalpha and soluble IL-6 receptor were also higher than in the control group. Patients on hemodialysis showed positive correlation between concentrations of MDA+4HNE and IL-6 and TNFalpha. CONCLUSION: The correlations found between the products of lipid peroxidation and proinflammatory cytokines suggest causative relation between the intensity of peroxidative processes and stimulation of immunological response in hemodialysed patients, which may increase the risk of atherosclerotic changes in those patients.     

辛伐他汀对维持性血液透析患者微炎症状态的影响

目的观察辛伐他汀对维持性血液透析患者微炎症状态的影响,探讨他汀类药物在治疗尿毒症患者微炎症状态中的作用。方法选择我院维持性血液透析患者60例,随机分为辛伐他汀治疗组和非辛伐他汀治疗组各30例。2组患者于治疗前,治疗后6个月检测高敏-C反应蛋白（hs-CRP）、白介素-6（IL6）、肿瘤坏死因子-α（TNF-α）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）水平;同时设42例健康者为健康对照组。结果①维持性血液透析患者hs—CRP、IL-6、TNF-α、TG水平显著高于健康对照者（P〈0．01）,HDL水平明显低于健康对照者（P〈0．05）;②治疗6个月后,辛伐他汀治疗组hs—CRP、IL-6、TNF-α、TG、TC、LDL的水平均有所下降,HDL升高,辛伐他汀治疗组hs—CRP、IL-6、TNF-α、TG、TC、LDL下降的水平与治疗前及非辛伐他汀治疗组相比,差异显著（P〈0．05）。结论辛伐他汀治疗能显著改善尿毒症患者的脂质代谢,同时改善患者的微炎症状态。     

Evaluation of lipid peroxidation and erythrocyte glutathione peroxidase and superoxide dismutase in hemodialysis patients

Oxidative stress often occurs in chronic hemodialysis (HD). The aim of the present study was to determine plasma malondialdehyde (MDA) level for lipid peroxidation product and erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities as enzymatic antioxidants. Thirty-one HD patients (aged 50.3 ± 14.9 years) who were dialyzed three times per week and 31 healthy subjects (aged 47.8 ± 13.9 years) were enrolled. The results showed lower enzymatic antioxidants activity (GPx, SOD) and higher MDA levels in comparison with control subjects. In addition, SOD and GPx activities significantly decreased and MDA increased after HD. We also found that there was a significantly negative correlation between SOD and GPx with MDA. The results suggest that elevated level of plasma MDA and reduced activities of SOD and GPx can be caused oxidative stress, which may play a critical role in HD complications.     

Serum paraoxonase activity in uremic predialysis and hemodialysis patients

BACKGROUND: Paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated enzyme and has been shown to reduce the susceptibility of low-density lipoprotein (LDL) to lipid peroxidation. This study aimed to investigate the activity and phenotype distribution of serum paraoxonase in uremic patients, and to evaluate the correlations of uremia-associated substances (urea, creatinine (Cr) and uric acid) with paraoxonase activity. METHODS: Twenty-eight patients with chronic renal failure (CRF), 44 patients with CRF undergoing hemodialysis (HD) and 26 healthy controls were included in this study. Paraoxon or phenylacetate was used as a substrate for measuring paraoxonase and arylesterase activity, respectively. The double substrate method was used to assign phenotypes. Serum lipid parameters were determined by routine laboratory methods. RESULTS: Paraoxonase activity, HDL-cholesterol and apolipoprotein (apo) AI levels were found to be significantly lower in HD patients than in controls. However, HDL-standardized paraoxonase activity (PON activity/HDL) was not different in the HD patients compared to controls. Arylesterase activity was significantly lower in both CRF and HD patients than in controls. Paraoxonase phenotype distribution was not different among the groups according to the double substrate method. Serum paraoxonase and arylesterase activities correlated inversely with serum urea and Cr levels. CONCLUSION: Patients on long-term HD have reduced paraoxonase/arylesterase activities and this could be related to reduced HDL-cholesterol and apo AI levels, as well as increased urea and Cr levels in uremia.     

Role of soluble receptors for tumor necrosis factor alpha in the development of hypoalbuminemia in hemodialysis patients

BACKGROUND: Hypoalbuminemia is a significant predictor of mortality in patients on hemodialysis (HD). The cause of hypoalbuminemia in HD patients, however, remains to be clarified. Recent studies have demonstrated that high blood concentrations of soluble receptors for tumor necrosis factor (sTNFRs) are associated with malnutrition in a variety of diseases and that the blood sTNFRs concentrations are elevated in HD patients. METHODS: The serum concentrations of tumor necrosis factor alpha, sTNFR (p55 and p80), and interleukin (IL) 6 were measured in 21 HD patients with low (equal to or less than 3.6 g/dl) and in 19 HD patients with normal (equal to or more than 4.0 g/dl) concentrations of serum albumin who were free from acute infection, malignancy, collagen diseases, liver diseases, or surgery. The correlation between these parameters and the degree of hypoalbuminemia was examined. RESULTS: The serum concentrations of sTNFR p80 and IL-6 were significantly higher in patients with hypoalbuminemia as compared with those with normoalbuminemia (sTNFR p80: 47.4 +/- 4.7 vs. 35.3 +/- 2.1 ng/ml, p < 0.05; IL-6: 10.8 +/- 2.0 vs. 6.3 +/- 0.5 pg/ml, p < 0.05). In contrast, there was no difference in the serum concentrations of tumor necrosis factor alpha and sTNFR p55 between the two groups. Multivariate regression analysis showed that sTNFR p80 but not IL-6 significantly influenced the serum albumin concentrations. There were no significant differences in body mass index, serum total cholesterol, and normalized protein catabolic rate between the two groups. CONCLUSIONS: Our results suggest the development of hypoalbuminemia in some HD patients who do not have any obvious cause of hypoalbuminemia and that high concentrations of sTNFR p80 might contribute to the development of hypoalbuminemia in patients on long-term HD.     

Lipid peroxidation and antioxidant state after laparoscopic and open cholecystectomy.

OBJECTIVE: To measure the amount of lipid peroxidation and erythrocyte antioxidation in patients undergoing laparoscopic and open cholecystectomy and healthy controls. DESIGN: Non-randomised study. SETTING: University hospital, Istanbul. SUBJECTS: 31 patients, of whom 14 underwent open and 17 laparoscopic cholecystectomy, and 15 healthy controls. INTERVENTIONS: Heparinised blood samples were taken from the patients immediately after operation and from the healthy controls. MAIN OUTCOME MEASURES: Lipid peroxidation index as expressed by thiobarbituric-acid-reactive substances (TBARS) and components of the erythrocyte antioxidant defence system, namely reduced glutathione, reduced glutathione peroxidase (glutathione-Px) and CuZn superoxide dismutase (CuZn SOD) in patients undergoing open or laparoscopic cholecystectomy and healthy controls. RESULTS: All 4 variables were significantly higher in the cholecystectomy groups than in controls (p < 0.001), and laparoscopic cholecystectomy caused significantly less oxidative stress than the open operation (p < 0.001). CONCLUSION: Both types of cholecystectomy cause oxidative stress and lead to an adaptive antioxidant response in the body. However; both oxidative stress and the antioxidant response are more pronounced after traditional open cholecystectomy.     

Smoking is associated with alterations of blood thiol-group related antioxidants in patients on hemodialysis

Cardiovascular disease is the major complication and cause of mortality in the dialysis population, accounting for about 40% of deaths. Oxidative stress has been strongly implicated in the pathogenesis of these events. As patients in end-stage renal disease (ESRD) are in a state of elevated free radical activity, the aim of the present study was to investigate the negative impact of smoking in 45 male hemodialysis (HD) patients. These patients, who were 40-85 years of age (mean age 60.9 +/- 13.3 years), had been on hemodialysis for at least 12 months before participating in this study. Fasting blood sampling for serum lipid, albumin, urate, lipid peroxides total blood glutathione (tGSH), non-GSH free sulfhydryl compounds (non-GSH fSH), plasma glutathione peroxidase (pGSHPx), erythrocytes glutathione peroxidase (rGSHPx), plasma glutathione S-transferase (pGST) and erythrocytes glutathione S-transferase (rGST) were determined. Our study showed that the plasma malonyldialdehyde (MDA) concentration was significantly higher in HD patients who smoked than in those who were non- smokers (1.99 +/- 0.53 vs. 1.55 +/- 0.46 nmol/ml, p = 0.008). No association was found between levels of MDA in smokers and BMI, serum cholesterol and triglycerides and smoking index. We also found that the circulating plasma levels of tGSH and non-GSH fSH was lower in the HD patients who smoked (tGSH 164.9 +/- 41.5 vs. 203.4 +/- 45.3 microg/ml; fSH 271.1 +/- 55.8 vs. 308.8 +/- 46.7 microg/ml; p < 0.05 and p < 0.001, respectively). There were no significant differences in the plasma levels of uric acid, pGSHPx, rGSHPx, pGST, rGST, albumin, and age between the 2 groups. Partial correlation analysis of the plasma levels of the measured antioxidants and the smoking index revealed a negative correlation between the plasma levels of tGSH and smoking index (r = -0.62, p < 0.003). Similarly, the plasma levels of tGSH was found negatively correlated with the levels of plasma MDA (r = -0.32, p < 0.05) of the HD patients. In conclusion, our data suggest that cigarette smoking has a negative impact on plasma-circulating products of lipid peroxidation in HD patients. The lower blood levels of the tGSH and non-GSH fSH in HD patients who smoked suggests that these patients may be more susceptible to oxidative damage caused by smoking.     

Relationships among inflammation nutrition and physiologic mechanisms establishing albumin levels in hemodialysis patients

BACKGROUND: Serum albumin concentration is a balance among its synthesis rate, fractional catabolic rate (FCR), distribution, dilution in the plasma pool and external loss. The physiologic bases for establishing the level of serum albumin in hemodialysis patients have not been defined despite the association of hypoalbuminemia with excess mortality. Albumin concentration is associated with the levels of several acute phase proteins (APPs), C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1 AG), or ceruloplasmin, and with nutritional markers, such as normalized protein catabolic rate (nPCR). METHODS: To establish the relationship among parameters that regulate albumin levels and markers of nutrition and inflammation, we injected [125I]-albumin, into 64 hemodialysis patients enrolled in the HEMO study to measure albumin distribution, synthesis and FCR. These variables were related to the levels of acute phase proteins (APPs), nPCR, body mass index (BMI), external albumin loss as well as demographic variables. Albumin distribution, synthesis and FCR were calculated from kinetic modeling, as was the initial plasma volume (PV). Serum albumin, transferrin, CRP, ceruloplasmin and alpha1 AG were measured weekly. Dialysate was collected during one dialysis each week to measure albumin loss. Results were analyzed by multiple linear regression. RESULTS: Albumin concentration correlated with its synthesis rate and FCR, but not with PV or its distribution between the vascular and extravascular pools. Albumin concentration also correlated with nPCR and alpha1 AG. However, albumin synthesis was directly related most strongly to PV and BMI (or nPCR), but not to levels of APPs. By contrast, albumin FCR correlated positively with both alpha1 AG and ceruloplasmin. CONCLUSION: Albumin concentration in dialysis patients changes with inflammation and nutritional status through their effects on albumin catabolism and synthesis, respectively. Within the range of albumin levels in these patients, nutritional variables primarily affected albumin synthesis while inflammation caused hypoalbuminemia by increasing albumin FCR. Albumin synthesis also increased in proportion to PV. The result of this is that PV expansion does not contribute to hypoalbuminemia.     

Serum antioxidant activity in uremic patients

Serum antioxidant activity (AOA) was examined in 35 healthy subjects and 111 patients with chronic renal failure (CRF), consisting of 13 patients in the predialysis stage, 11 requiring the start of regular dialysis therapy (RDT) and 87 undergoing RDT. Serum AOA was determined by assaying serum activity to inhibit malondialdehyde (MDA) generation. AOA levels were significantly lower in CRF patients, and the lowest levels were noticed in patients with uremic symptoms requiring the start of RDT. These levels were restored to a subnormal level during RDT. Defective serum AOA appears to be an endogenous metabolic consequence in uremia. Sera with low AOA tended to show high MDA levels, indicating that patients with low serum AOA were susceptible to cellular injury by lipid peroxidation. It is proposed that defective serum AOA may contribute to a certain uremic toxicity through peroxidative cell damage.     

The hematocrit-corrected erythrocyte sedimentation rate can be useful in diagnosing inflammation in hemodialysis patients.

BACKGROUND/AIMS: We aimed to determine predictors of erythrocyte sedimentation rate (ESR), and the ESR level pointing to the presence of inflammation in 60 chronic hemodialysis (HD) patients. METHODS/RESULTS: On bivariate analysis, increased Westergren ESR of 62 (4-160) mm/h correlated inversely with hematocrit (Hct) and serum albumin, and positively with age, plasma fibrinogen, serum C-reactive protein (CRP), immunoglobulins A and G, alpha(1)-acid-glycoprotein and alpha(1)-antitrypsin. On multivariable analysis, independent predictors of the ESR were raised CRP (p < 0.0001), low Hct (p < 0.0001), increased fibrinogen (p < 0.0001) and immunoglobulin A (p = 0.009), and older age (p = 0.015). The Hct-corrected ESR level [ESR x (Hct/45)] of 38 (4-91) mm/h was independently predicted by CRP (p < 0.0001), fibrinogen (p < 0.0001), and age (p = 0.001). In the patients with normal CRP and albumin, the Hct-corrected ESR value was normal (23 mm/h) and lower than that of 59 mm/h in the subjects with elevated CRP and hypoalbuminemia. Using these cut-off points, the positive and negative predictive values of the Hct-corrected ESR on the presence of inflammation were 1.0, and its sensitivity and specificity were 100%. CONCLUSION: Increased Westergren ESR in HD patients is associated with activated acute-phase response, anemia, and aging. The Hct-corrected ESR values of 23 and 59 mm/h precisely select the HD patients with severe inflammation from those without.     

The morphofunctional damage to the biomembranes in the lipid peroxidation syndrome in patients with the terminal stage of chronic kidney failure

A total of 43 patients with a terminal stage of chronic renal failure (TCRF) who were on planned hemodialysis 8-12 hrs per week were studied for the status of lipid peroxidation, antioxidative system (AOS) as well as for the morphological and functional status of biological membranes. The study revealed high levels of lipid peroxidation featured by increased contents of malonic dialdehyde (MDA) and diene conjugates in the blood serum and red cells of the uremic patients. Besides, the functional incompetence of a nonenzymatic part of the AOS resulting in a decrease in the number of sulfhydryl groups in the red cells and alphatocopherol in the plasma was documented. It was suggested that intense peroxidation of lipids could lead to morphological and functional instability of biological membranes in the TCRF patients that was evidenced by high peroxide hemolysis in the red cells and disordered osmotic resistance and deformability of erythrocytes. An active MDA clearance was revealed in hemodialysis. The use of antioxidants and membraneous protectors in the treatment of the TCRF patients was found to be mandatory when high lipid peroxidation was identified.     

Effects of vitamin C infusion and vitamin E-coated membrane on hemodialysis-induced oxidative stress

Chronic hemodialysis (HD) patients manifest anemia and atherosclerosis with associated oxidative stress. We explored whether intravenous infusion of vitamin C (VC) and/or use of vitamin E (VE)-coated dialysis membrane could palliate HD-evoked oxidative stress. Eighty patients undergoing chronic HD were enrolled and randomly assigned into four groups: HD with intravenous VC (n=20), HD with VE-coated dialyzer (n=20), HD with both (n=20), and HD with neither (n=20). We evaluated oxidative stress in blood and plasma, erythrocyte methemoglobin/ferricyanide reductase (red blood cells (RBC)-MFR) activity, plasma methemoglobin, and pro-inflammatory cytokines in these patients. All patients showed marked increases (14-fold) in blood reactive oxygen species (ROS) after HD. The types of ROS were mostly hydrogen peroxide, and in lesser amounts, O2*- and HOCl. HD resulted in decreased plasma VC, total antioxidant status, and RBC-MFR activity and increased plasma and erythrocyte levels of phosphatidylcholine hydroperoxide (PCOOH) and methemoglobin. Intravenous VC significantly palliated HD-induced oxidative stress, plasma and RBC levels of PCOOH, and plasma methemoglobin levels and preserved RBC-MFR activity. The VE-coated dialyzer effectively prevented RBCs from oxidative stress, although it showed a partial effect on the reduction of total ROS activity in whole blood. In conclusion, intravenous VC plus a VE-coated dialyzer is effective in palliating HD-evoked oxidative stress, as indicated by hemolysis and lipid peroxidation, and by overexpression of proinflammation cytokines in HD patients. Using VE-coated dialyzer per se is, however, effective in reducing lipid peroxidation and oxidative damage to RBCs.     

Red blood cell membrane lipid peroxidation in continuous ambulatory peritoneal dialysis patients

We have recently described that in the erythrocytes from uremic patients on chronic hemodialysis, the pentose-phosphate shunt is defective, the membrane concentrations of malonyldialdehyde, resulting from peroxidation of polyunsaturated fatty acids in the membranes themselves, are increased, and the concentrations of vitamin E, an antioxidizing agent, are reduced. In the present study we have analyzed these same metabolic aspects in a group of uremic patients in continuous ambulatory peritoneal dialysis. We have found normal function of the pentose-phosphate shunt, slightly elevated concentrations of malonyldialdehyde compared to controls, but definitely lower than in chronic hemodialysis patients, and higher tocopherol concentrations than in both controls and chronic hemodialysis patients.     

Evidence for increased lipid peroxidative damage and loss of superoxide dismutase activity as a mode of sublethal cryodamage to human sperm during cryopreservation.

Cryopreservation of human sperm, now generally required in donor insemination programs, adversely affects the sperm in terms of standard sperm evaluation parameters and fertilizing ability. The freeze-thaw process appears to produce sublethal damage that appears only after a delay. The authors hypothesized that cryopreservation enhanced peroxidation of sperm membrane lipids, based on previous studies of sperm lipid peroxidation, which showed that the effects of peroxidative damage became evident only after a delay, depending on the peroxidation rate. The effect of cryopreservation on the phospholipid content, the composition of the acyl moieties of the phospholipids, and the activities of the peroxidation protective enzymes, superoxide dismutase (SOD) and glutathione peroxidase plus reductase, in human sperm were examined to test the hypothesis. Parallel determinations were made of the percent motility, the average path velocity of the motile cells, and the time to loss of motility under specified aerobic incubation conditions, which gives a good estimate of the lipid peroxidation rate. The phospholipid content decreases after cryopreservation, with loss of phosphatidylcholine and phosphatidylethanolamine being the more pronounced. Polyunsaturated acyl moieties were also preferentially lost. This loss pattern is observed also from lipid peroxidation. The activities of glutathione peroxidase plus reductase remained unchanged. The sperm SOD activities varied widely between samples before cryopreservation. In all samples there was a decline in SOD activity after freeze-thaw, but the extent of the decline was also widely variable. The time to loss of motility declined in parallel with SOD activity, and a strong correlation (R2 greater than 0.9) between SOD activity and time to loss of motility was found for all samples, before and after freeze-thaw. The authors conclude that cryopreservation does enhance lipid peroxidation in human sperm, as hypothesized, and that this enhancement is mediated at least in part by the loss of SOD activity occurring during the process.