Comparison of effect of vitamin E-coated dialyzer and oral vitamin E on hemodialysis-induced Cu/Zn-superoxide dismutase

BACKGROUND: We reported earlier that production of Cu/Zn-superoxide dismutase (SOD) increases markedly in hemodialysis patients but not in non-dialyzed chronic renal failure (CRF) patients. In this study, we compared the antioxidant effects of oral vitamin E supplementation (VE-PO) and vitamin E coating of a dialyzer (VE-BMD) by measuring increased Cu/Zn-SOD in hemodialysis patients. METHODS: 31 hemodialysis patients were divided into two groups: 16 hemodialysis patients underwent usual dialysis with vitamin E supplementation 600 mg/day while 15 others were dialyzed using vitamin E-coated membrane for 6 months. Total plasma SOD activity was determined by NBT method, plasma Cu/Zn-SOD contents by ELISA and Cu/Zn-SOD mRNA in leukocytes by RT-PCR. RESULTS: VE-PO and VE-BMD showed almost comparable effects on Cu/Zn-SOD contents and its mRNA levels in hemodialysis patients. VE-PO resulted in a progressive decrease of Cu/Zn-SOD content (p < 0.001). A comparable progressive decrease was observed also in VE-BMD (p < 0.0001). Both VE-PO and VE-BMD resulted in a progressive decrease of Cu/Zn-SOD mRNA (p < 0.01), which reached the level of non-dialyzed CRF patients.     

Trace elements and lipid peroxidation abnormalities in patients with chronic renal failure

Plasma selenium (Se), zinc (Zn) and copper (Cu) levels and antioxidant metalloenzymes, glutathione peroxidase (GPX) and superoxide dismutase (SOD), were studied in 17 patients on maintenance hemodialysis (HD) (group I), 14 uremic patients (group II) and 14 healthy subjects (group III). Plasma Se levels and erythrocyte GPX were significantly lower in the HD group (for Se: 0.69 +/- 0.12 vs. 1.05 +/- 0.13 mumol/l in controls; for erythrocyte GPX: 34.4 +/- 6.4 vs. 49.2 +/- 9 IU/g hemoglobin in controls) and a significant correlation was found between the two parameters (r = 0.66, p less than 0.005). There was also a correlation between decreased plasma Zn and erythrocyte SOD activity (r = 0.58, p less than 0.02) and between decreased plasma Cu and erythrocyte SOD (r = 0.60, p less than 0.02). Plasma malondialdehyde levels were augmented in HD patients (5.08 +/- 0.26 vs. 2.55 +/- 0.15 mumol/l in controls and 2.79 +/- 0.40 mumol/l in the uremic group). The catalase activity was increased in HD patients (202 +/- 24 vs. 140 +/- 40 IU/mg hemoglobin in group III). A defective antioxidant activity may thus contribute to increased peroxidative damage to cells in the course of dialysis.     

Lipid peroxidation and antioxidant enzymes in children with chronic renal failure

Increased lipid peroxidation (LP) has been observed in dialysis patients and in predialysis adults with advanced chronic renal failure (CRF). The aim of this study was to investigate whether predialysis CRF children have increased LP in plasma and red blood cells (RBC) and to evaluate the activity of the antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)] in RBC. Concentrations of selenium (Se), copper (Cu), and zinc (Zn)—cofactors of these enzymes—were determined both in erythrocytes and in plasma. LP was monitored by plasma and erythrocyte malonyldialdehyde (MDA) and by plasma organic hydroperoxide (OHP) concentrations. Forty-six predialysis children, aged 5–18 years, divided into two groups according to their serum creatinine levels [group I (n=14, mean serum creatinine 421.61±141.08 mol/l), group II (n=32, mean serum creatinine 174.94±45.50 mol/l)] and 27 age-matched healthy subjects were enrolled in the study. Significantly higher concentrations of plasma and erythrocyte MDA and plasma OHP, significantly lower activities of GSH-Px and CAT, and significantly lower concentrations of erythrocyte Se, Cu, and Zn and plasma Se and Cu were found in both groups of renal patients compared with controls. The SOD activity was reduced in both groups of CRF children. In group I the activity of SOD and GSH-Px was significantly lower than in group II. In summary, there is increased LP in plasma and RBC in children with predialysis CRF, even those patients with moderate renal insufficiency. The activity of the enzymatic antioxidant defense system is reduced in the RBC of predialysis patients. The antioxidant capacity is related to the severity of renal failure.     

Impact of acute renal failure on antioxidant status in multiple organ failure

BACKGROUND: Acute renal failure (ARF) can be triggered or aggravated by reactive oxygen species (ROS) but established ARF per se might also affect the antioxidant defence mechanisms of the organism. We evaluated a broad pattern of antioxidants in critically ill patients with multiple organ failure with (MOF-ARF) and without acute renal failure (MOF) to identify any potential involvement of renal dysfunction in the depletion of the antioxidant system. METHODS: Observational study; 13 patients with MOF were investigated (9 with and 4 without ARF), and 17 healthy subjects served as controls. Blood samples were drawn after establishment of MOF. Plasma levels of ascorbate, alpha-tocopherol, retinol, beta-carotene, selenium and lipid peroxidation products (MDA) were determined and the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione-peroxidase (GSH-PX) in erythrocytes were measured. In addition, ROS production (superoxide anion and hydrogen peroxide) in activated neutrophils was assessed. RESULTS: Plasma levels of ascorbate, beta-carotene and selenium were reduced in both patient groups, when compared to controls. Decrease in selenium was more pronounced in the MOF-ARF group. MDA levels were increased in both groups, again being more pronounced in MOF-ARF patients compared to MOF patients. Hydrogen peroxide production by neutrophils from both patient groups was lower than from controls. CONCLUSION: A depression of the antioxidative system is present in critically ill patients with MOF. In patients with associated ARF this was even more pronounced and plasma MDA levels were higher, suggesting an additional effect on the antioxidative potential in the presence of renal dysfunction and/or renal replacement therapy.     

Iron and oxidative stress in renal insufficiency

BACKGROUND/AIMS: Iron (Fe) can cause tissue injury and oxidative stress by catalyzing hydroxyl radical production and lipid peroxidation. Intravenous (i.v.) Fe preparations are routinely administered to treat anemia in patients with chronic renal failure (CRF), a condition marked by oxidative stress and inflammation. In an earlier study, we showed that iron overload augments oxidative stress in the cardiovascular tissues of CRF rats. This study was designed to expand these observations to other major organs. METHODS: Rats were randomized into CRF (5/6 nephrectomized) and sham-operated control (CTL) groups. Each group was subdivided into Fe-loaded (single i.v. injection of iron dextran complex, 0.5 g/kg) and placebo-treated subgroups. After 13 weeks, systolic blood pressure, blood hemoglobin (Hb), plasma Fe concentration, lipid peroxidation products, superoxide generating enzyme, NAD(P)H oxidase, and antioxidant enzymes were determined. RESULTS: Systolic blood pressure was equally elevated and creatinine clearance was equally reduced in both CRF groups. Fe administration raised Hb, serum Fe and transferrin saturation in both CRF and CTL groups. The plasma concentration of lipid peroxidation product, malondialdehyde, was increased by Fe injection in CRF rats but not the control group. Renal tissue abundance of gp91(phox) subunit of NAD(P)H oxidase was elevated in the untreated CRF group and was partially reduced in the iron dextran-treated CRF group. Tissue abundance of the antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were decreased in both untreated and iron dextran-treated CRF groups. CONCLUSION: CRF resulted in marked SOD, CAT and GPX deficiencies. A single i.v. administration of iron dextran in rats with CRF induced oxidative stress as measured by increased lipid peroxidation products and decreases in antioxidant enzymes.     

Phagocytic activity and oxygen radicals production of neutrophils in patients with chronic renal failure

As disorders of the defense mechanism in hemodialysis (HD) patients, impairments of cell-mediated immunity have been known, but no agreement has yet been reached as to the function of their polymorphonuclear leukocytes (PMN). Thus this study was undertaken to determine the phagocytic activity and oxygen radicals production of PMN in patients with chronic renal failure (CRF). It was demonstrated that the phagocytic activity of PMN was significantly decreased in HD patients as compared with that in healthy subjects. A significant correlation was also found between phagocytic activity and FcR-positive cells of PMN in HD patients. It suggested that the FcR status of PMN might play an important role with phagocytic activity in HD patients, and the decrease of FcR-positive PMN affects the drop with phagocytic activity. Hydrogen peroxide production of prepared PMN was not significantly different for CRF patients versus healthy subjects. But in whole blood, the enhanced hydrogen peroxide production was observed in all CRF patients. And it was also demonstrated that PMN hydrogen peroxide production become strikingly enhanced when normal PMN was suspended in plasma from CRF patients. When normal renal function was restored by transplantation, hydrogen peroxide production was normalized. These results strongly suggested that the presence of the hydrogen peroxide production enhancing factor in plasma from CRF patients and the enhanced hydrogen peroxide production were specifically associated with renal dysfunction. In plasma of HD patient treated with the EVAL membrane, we measured the hydrogen peroxide production both before and after dialysis. The plasma of postdialysis showed slightly lower hydrogen peroxide production than that of predialysis in most of patients. It was also demonstrated that the plasma from CAPD patients showed a lower hydrogen peroxide production than that from other CRF patients. These results suggested that the hydrogen peroxide production enhancing factor could be considered as one of so called the middle molecules.     

Plasma glutathione peroxidase activity is reduced in haemodialysis patients

Cardiovascular disease is the major cause of morbidity and mortality in patients with end-stage renal failure. Increased free radical production and antioxidant depletion may contribute to the greatly increased risk of atherosclerosis in these patients. Glutathione peroxidase (GPX) is an important antioxidant, the plasma form of which is synthesized mainly in the kidney (eGPX). The aim of this study was to assess the activity of eGPX in patients with end-stage renal failure on haemodialysis. Venous blood was collected from 87 haemodialysis patients immediately prior to and after dialysis and from 70 healthy controls. Serum eGPX activity was measured using hydrogen peroxide as substrate and immunoreactivity determined by ELISA. eGPX activity was significantly reduced in dialysis patients when compared to controls (106 +/- 2.7 and 281 +/- 3.6 U/l respectively, p < 0.001). Following haemodialysis, eGPX activity rose significantly to 146 +/- 3.8 U/l, p < 0.001, although remaining below control values (p < 0.005). Immunoreactive eGPX, however, was similar in all groups (pre-dialysis 14.10 +/- 1.26 microg/ml, post-dialysis 14.58 +/- 1.35 microg/ml, controls 15.20 +/- 1.62 microg/ml, p = NS). A decrease was observed in the specific activity of eGPX in patients when compared to controls (8.81 +/- 1.14, 10.71 +/- 1.54 and 21.97 +/- 1.68 U/mg respectively, p < 0.0001). eGPX activity is impaired in patients undergoing haemodialysis and so may contribute to atherogenesis in renal failure.     

Renal cortical thickness and PON1 activity both decrease in chronic renal failure

BACKGROUND: Chronic renal failure (CRF) is associated with a tendency to atherosclerosis due to the enhanced oxidative stress and insufficient antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and paraoxonase (PON 1), together with abnormalities in lipid parameters. We determined the in vitro susceptibility of low-density lipoprotein (LDL) to oxidation and PON1 activities in patients with chronic renal insufficiency to see how PON1 affected the progression of the disease and whether hemodialysis influenced these parameters. METHODS: Thirty-seven patients (21 men, 16 women, mean age 43.9 +/- 16) with CRF were included, 23 were receiving hemodialysis treatment. Exclusion criteria were diabetes mellitus and acute coronary disease. Eighteen healthy subjects (9 men and 9 women, mean age 39.9 +/- 10.5) volunteered to participate as controls. All patients were evaluated by renal ultrasound (USG) and two-dimensional echography, and their lipid profiles, PON1 activity, basal and Cu-induced LDL oxidation were determined. RESULTS: PON1 activities of patients were lower than controls (14.4 +/- 11 vs 30.9 +/- 19 U/L, p < 0.05) while basal ox-LDL levels determined by the thiobarbituric acid reactive substances (TBARS) method were higher (0.6 +/- 0.4 vs 0.4+/- 0.2 nmol/mg LDL protein, p<0.01). There was no significant difference between the groups treated with hemodialysis or not. There was a positive correlation between renal cortical thickness and HDL levels (r=0.47, p=0.006) and PON1 activity (r=0.45, p=0.01). CONCLUSION: Our data showed that HDL cholesterol levels and PON1 activities were both lower in patients, indicating depletion of the protective antioxidant capacity. PON1 activities and phenotypes were no different in patients with coronary disease and others so it does not appear to be a significant indicator of coronary artery disease in patients with CRF.     

The association of oxidant–antioxidant status in patients with chronic renal failure

Oxidative stress has been linked to disease progression, including chronic renal failure (CRF). The aim of the present study was to determine malondialdehyde (MDA) as a sign of lipid peroxidation, and to investigate the association between antioxidant activities and three trace elements, in 49 patients with CRF. The erythrocyte and plasma trace elements [selenium (Se), zinc (Zn), and copper (Cu)] and antioxidant defense levels were determined: glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), vitamins E and C. The obtained values were compared with 42 age- and sex-matched healthy controls. There were significantly lower mean values of plasma Se, GPx, vitamins E and C, erythrocyte Se, SOD and CAT levels in the patient group compared to the control group (p?相似文献   

Human atrial natriuretic peptide in non-dialyzed patients with chronic renal failure

The role of human atrial natriuretic peptide (alpha-hANP) in the regulation of blood pressure (BP) and extracellular fluid volume (ECFV) remains elusive. This is of particular interest in chronic renal failure, in which first, increased sodium and water retention plays a major pathogenetic role in the development of hypertension, and second, altered secretion and/or metabolism of alpha-hANP may contribute to fluid volume and BP regulation. In the present study the relationship between renal function, BP, and circulating alpha-hANP was investigated in 16 non-dialyzed patients with stable chronic renal failure (CRF) without edema. Analysis of potential molecular heterogeneity of immunoreactive (ir) ANP was performed by gel permeation chromatography of plasma extracts from normotensive patients with CRF. Serum creatinine concentrations averaged 435 +/- 76 mumol/l ranging from 127 to 1187 mumol/l, systolic and diastolic BP averaged 158 +/- 4 and 94 +/- 2 mmHg, respectively. Plasma alpha-hANP concentrations ranged from 5 to 75 with a mean of 23 +/- 4 pmol/l as compared to a mean of 10 +/- 1 pmol/l in healthy volunteers (p less than 0.05). A significant linear correlation between plasma alpha-hANP and serum creatinine concentrations (r = 0.92) was observed; a weaker correlation was found between mean arterial pressure and alpha-hANP (r = 0.66). Chromatographic analysis revealed considerable amounts of higher molecular weight circulating ir-ANP, approximately 15,000 Da, in addition to the biologically active small mol wt ANP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Time course of antioxidant enzyme activities in liver transplant recipients

Reactive oxygen species (ROS) play a central role in ischemia-reperfusion injury after organ transplantation. They are degraded by endogenous radical scavengers such as antioxidant enzymes. The purpose of this study was to evaluate the temporal variations of antioxidant enzyme activities in liver transplant recipients. The study was performed in 13 liver transplant patients (11 men and 2 women). Blood samples were obtained pre- and postsurgical intervention: before transplant (T(0)), and 1, 6, 12, 24, 48, and 72 hours, as well as 5 and 7 days thereafter. We determined total and specific superoxide dismutase (SOD) activity, catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR) activities as well as malondialdehyde (MDA) and low-density lipoproteins (LDL). The results showed increased SOD and mainly GPX activities after liver transplantation, which correlated with MDA levels. Total SOD activity was mainly represented by Mn-SOD (75%) and Cu,Zn-SOD (25%), whereas Fe-SOD was not detected. In conclusion, the enhanced antioxidant enzyme activities reported in this study indicated a control of oxidative stress generated in liver transplantation. In this sense, although MDA levels showed an enormeous increase at 1 hour after transplantation, the lipid peroxidation was compensated for by GPX activity.     

Increased oxidative stress and oxidative damage associated with chronic bacterial prostatitis

目的:探讨慢性细菌性前列腺炎是否会在患者体内引起氧化应激加剧和氧化损伤及其可能的机理。方法:采用病例对照研究设计,用分光光度分析法检测了随机纳入的70例慢性细菌性前列腺炎患者(CBPP)与70例健康成人志愿者(HAV)的血浆一氧化氮(NO),维生素 C(VC)、维生素 E(VE)和β-胡萝卜素(β-CAR)水平以及红细胞丙二醛(MDA)水平,超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPX)活性。结果:与 HAV 组相比较,CBPP 组的血浆 NO 和红细胞 MDA 的均值显著增高(P<0.001),血浆 VC、VE 和β-CAR 及红细胞 SOD、CAT 和 GPX 活性均值显著降低(P<0.001)。70例 CBPP 的偏相关分析结果提示,随着病程的延长,NO 和 MDA 值逐渐增高(P<0.001),VC、VE、β-CAR、SOD、CAT 和 GPX 值逐渐降低(P<0.05-0.001)。70例 CBPP 的逐步回归提示其模型为 Y=-13.2077 0.1894MDA 0.0415NO-0.1999GPX,F=18.2047,P<0.001,r=0.6729,P<0.001。结论:本研究结果提示,患者体内存在着由慢性细菌性前列腺炎引起的氧化应激加剧和氧化损伤,且这种现象与患者的病程密切相关。     

Evaluation of oxidative stress after repeated intravenous iron supplementation

Parenteral iron has been recommended for the treatment of iron deficiency in the majority of maintenance hemodialyzed (HD) patients. However, iron supplementation and consequent over saturation of transferrin and high iron levels, may aggravate oxidative stress already present in these patients. This study aimed to further clarify the role of repeated intravenous iron therapy as a supplementary cause of oxidative stress in HD patients. Markers of free radical activities (carbonyl reactive derivatives, CRD, thiol groups, SH, malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase, SOD and glutathione peroxidase, GPX) were determined in plasma and red blood cells (RBC) of 19 hemodialysis patients given a total iron dose of 625 mg (ferrogluconat, Ferrlecit, 62.5 mg). Blood samples were taken before the first and after the last dose of iron. Twenty apparently normal subjects served as healthy controls. Before iron treatment, HD patients exhibited increased concentrations of MDA and CRD in plasma and red blood cells, accompanied with impaired antioxidant capacity. All patients responded to iron therapy with a significant increase in their serum ferritin, serum iron, hemoglobin, and red blood cells levels. However, iron treatment resulted in enhanced oxidative stress in plasma of HD patients, since significant increase in plasma MDA and CRD concentrations, together with a decrease in nonprotein SH groups levels were detected. Supplementation with iron did not significantly influence plasma SOD and GPX activities, nor did any of the red blood cell parameters tested. Our data show that, despite improvement in hematological parameters, an increase in iron stores due to supplementation could also contribute to increased free radical production in HD patients.     

Epoetin treatment improves red blood cell and plasma antioxidant capacity in hemodialysis patients

The efficiency of human recombinant epoetin in alleviating anemia in hemodialyzed patients has been well documented. However, the effects of rhEPO therapy in correction of antioxidant capacity are not completely explained. In this study we examined both extracellular (plasma) and intracellular (red blood cells) antioxidant potential in hemodialyzed patients before and after three and six months of epoetin treatment by evaluating markers of oxidative stress (malondialdehyde) and antioxidant capacity (thiol groups, superoxide dismutase, and glutathione peroxidase). Six months of treatment with epoetin was followed by significant increases in thiol groups, superoxide dismutase and glutathione peroxidase activities in both plasma and red blood cells of hemodialyzed patients. Hence, during accelerated erythropoiesis, an increase in the number of young hematopoietic cells may replenish erythrocyte superoxide dismutase and glutathione peroxidase activity. However, the consequences of an imbalance between enzymatic antioxidant system (higher superoxide dismutase and lower glutathione peroxidase activity) that exists in these patients are the very high red blood cell and plasma malondialdehyde levels. These results suggest that, in spite of epoetin treatment and improvement in red blood cells and plasma antioxidant capacity, the production of reactive oxygen species overwhelms the intracellular and extracellular antioxidant capacity.     

Increased plasma malondialdehyde levels in glomerular disease as determined by a fully validated HPLC method.

BACKGROUND: Reactive oxygen species and particularly free radical induced lipid peroxidative tissue damage have been implicated in the pathogenesis of various renal diseases. Lipid peroxidation is assessed indirectly by the measurement of secondary products, such as malondialdehyde (MDA), using the widely employed thiobarbituric acid reactive substances (TBARS) method. However, this method lacks sensitivity and specificity. We have therefore developed and validated an HPLC (high-performance liquid chromatography) method for measurement of MDA and applied this to a variety of plasma samples in renal patients. METHODS: The optimized method involves antioxidant treatment of the plasma sample, followed by a protein precipitation step using trichloroacetic acid, acid hydrolysis and formation of an MDA thiobarbituric acid complex. The MDA-(TBA)2 adduct is separated from other interfering compounds by C18 reverse-phase HPLC techniques, with visible detection at 532 nm. RESULTS: The assay was linear over the ranges 0.25-1.0 microM MDA and the detection limit was 0.06 microM MDA. Within-run precision was <4.5% and between-run precision was <10.0%. MDA plasma concentrations (mean+/-SD) were higher in ESRF diabetic patients (0.32 +/- 0.14 microM, n=20), non-diabetic ESRF patients (0.32 +/- 0.09 microM, n=20), and CRF patients (0.14 +/- 0.06 microM, n=40) compared to healthy controls (0.11 +/- 0.03 microM, n=40), (P < 0.001, P < 0.001 and P = 0.008). Levels were similar in healthy controls with normal renal function and transplanted patients (0.12 +/- 0.03 microM MDA, n=40), (P=NS). No correlation was observed between MDA and creatinine levels (r2 = 0.05, n=80), which suggests that MDA does not correlate with the degree of renal impairment. We matched CRF patients with glomerular and non-glomerular causes of renal failure for creatinine levels and found that MDA levels were higher in patients with glomerulonephritis (0.16 +/- 0.06 microM) than in those with CRF from non-glomerular causes (0.12 +/- 0.04 microM, P = 0.002). CONCLUSIONS: We have introduced a reliable and sensitive HPLC technique to enhance the specificity of MDA-(TBA)2 measurement, with a significant improvement in HPLC column life. Using this method, picomole quantities of MDA can be detected in plasma. We have shown that MDA levels are significantly raised in patients with CRF due to glomerulonephritis, regardless of serum creatinine, which suggests that there is oxidative injury independent of any possible MDA retention due to renal impairment.     

The effect of dehydroepiandrosterone on renal ischemia-reperfusion-induced oxidative stress in rabbits

Reactive oxygen species (ROS) can play an important role in the pathogenesis of ischemia-reperfusion (I/R) injury. Dehydroepiandrosterone (DHEA) is one of the hormones secreted from adrenal glands, and in some studies it has been shown that DHEA has antioxidant properties. This experimental study was designed to determine the effect of DHEA on I/R-induced oxidative stress in rabbit kidney. Twenty-one rabbits were divided into three groups. Rabbits were subjected to 60 min of left renal pedicle occlusion followed by 24 h of reperfusion. DHEA (50 mg/kg) (I/R + DHEA group) or equal volume of vehicle (I/R group) was administered 3 h prior to ischemia. The control group received only laparotomy without I/R, DHEA or vehicle. At the end of the reperfusion periods, rabbits were decapitated. Renal tissues were taken for determination of malondialdehyde (MDA) levels as an indicator of lipid peroxidation and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities as antioxidant enzymes. In the I/R group, while renal SOD and CAT activities were significantly lower, MDA levels were significantly higher than in the I/R + DHEA group and controls. In the I/R + DHEA group, enzyme activities and MDA levels were similar to the controls. There was no significant difference in terms of renal GPX activity among the groups. DHEA may have a beneficial effect on renal tissue against oxidative damage due to I/R by preventing decreases in some antioxidant enzyme activities.     

IgA肾病患者血浆褪黑素水平与氧化应激的关系

目的：探讨 IgA 肾病肾功能正常患者血浆褪黑素水平与氧化应激的关系,为褪黑素用于治疗 IgA 肾病提供科学依据。方法：分为健康对照组（n =22）及 IgA 肾病肾功能正常组（n =48）。采用酶联免疫吸附法（ELISA）测定各组血浆褪黑素水平及分光光度法测定各组血浆丙二醛（MDA）、超氧化物歧化酶（SOD）水平。结果：与正常对照组相比,IgA 肾病肾功能正常组患者血浆褪黑素降低[（64．05±29．23）ng/ L vs．（80．54±35．12）ng/ L,P 〈0．05],而血浆 MDA 水平升高[（45．17±26．47）U/ ml vs．（31．14±26．00）U/ ml,P 〈0．05],血浆 SOD 水平下降[（76．25±19．34）U/ ml vs．（86．71±18．55）U/ ml,P 〈0．05）。进一步分析结果显示,IgA 肾病患者血浆褪黑素水平与 MDA 水平呈负相关（r =-0．308,P 〈0．05）,与 SOD 水平呈正相关（r =0．321,P 〈0．05）。结论：IgA 肾病肾功能正常患者血浆褪黑素水平较健康人降低,血浆 MDA 水平随血浆褪黑素水平降低而升高,血浆 SOD 水平随血浆褪黑素水平降低而降低。提示血浆褪黑素水平的降低引起机体抗氧化能力的下降,进而参与了 IgA 肾病的进展。补充外源性褪黑素可能为治疗 IgA 肾病具有潜力的方法。     

Vitamin E-coated dialyzer and antioxidant defense parameters: three-month study

Atherosclerotic cardiovascular disease is the most frequent cause of death in patients with end-stage renal disease who have undergone dialysis treatment. Oxidative stress, increased lipid peroxidation, and impaired function of antioxidant systems may contribute to the accelerated development of atherosclerosis in chronic renal failure patients during renal replacement therapy. The aim of this study was to investigate the influence of a vitamin E-coated dialyzer on antioxidant defense parameters in hemodialysis (HD) patients. In 14 HD patients, hemodialysis was performed using a vitamin E-coated dialyzer (Terumo CL-E15NL; Terumo Corporation, Tokyo, Japan) during a 3-month study. In these patients, erythrocyte (ER) antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR) and catalase (CAT), plasma total antioxidant capacity (TAC), RBC glutathione (GSH), plasma malondialdehyde (MDA), plasma, and RBC vitamin E were investigated. Each parameter was measured at the beginning of the study, after the 1st, 2nd, and 3rd month of the study, and 10 weeks after the interruption of the use of vitamin E-coated dialyzer. All HD patients were treated by erythropoietin (EPO) and received vitamin C 50 mg/d, pyridoxine 20 mg/d, and folic acid 5 mg/wk during the entire study. The 3-month treatment with the vitamin E-coated dialyzer led to a significant decrease of plasma MDA level (from 2.85 +/- 0.44 to 2.25 +/- 0.37 micromol/L) and to an increase of plasma TAC, RBC, GSH, and the vitamin E levels both in plasma (from 25.9 +/- 2.8 to 33.6 +/- 3.8 micromol/L) and in the RBCs (from 6.7 +/- 0.8 to 7.4 +/- 0.7 micromol/L) by 30% and 10.5%, respectively. Ten-week interruption of the use of the vitamin E-coated dialyzer led to near initial values of MDA (2.90 +/- 0.28 micromol/L), plasma (28.6 +/- 3.5 micromol/L), and RBC (6.9 +/- 0.7 micromol/L) vitamin E and of other investigated parameters. Statistical analysis of results was performed by conventional methods and analysis of variance. The findings of the current study confirm the beneficial effect of the vitamin E-coated dialyzer against oxidative stress in HD patients.     

Influence Of Chronic Exercise On Red Cell Antioxidant Defense,Plasma Malondialdehyde And Total Antioxidant Capacity In Hypercholesterolemic Rabbits

Despite the knowledge on the antiatherogenic effects of exercise, the mechanism by which exercise reduces atherogenic risk remains unknown. In this study, we investigated the hypothesis that chronic exercise-induced oxidative stress may increase plasma total antioxidant capacity and antioxidant defense in the red cells. For 8 weeks, 60 male Dutch rabbits were fed rabbit chow with or without the addition of 2% cholesterol. The animals were further divided into rest and exercise groups (n = 15 for each group). Animals in exercise groups ran on a rodent treadmill at 15 m/min for 10 to 60 minutes gradually for 5 days per week for a total of 8 weeks. At the end of experiments, blood samples were collected and glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) activities were determined in red blood cells. Total antioxidant capacity (TAC), malondialdehyde (MDA) and total thiol (T-SH) levels were measured in plasma. Thoracic aorta and carotid arteries were isolated for histological examination to evaluate atherosclerosis. Eight weeks of chronic exercise reduced atherogenic diet-induced atherosclerotic lesions in all the arteries studied, along with positive changes in cholesterol profile, especially increase of serum HDL-C level. Plasma MDA, TAC and T-SH concentrations were enhanced by exercise in both control and hypercholesterolemic diet groups. Erythrocyte catalase activity was significantly increased by chronic exercise (p < 0.05), whereas total SOD activity rose with exercise only in the control group. Surprisingly, GPX activity was significantly reduced (P < 0.05) in response to exercise in the control group and also in the high cholesterol diet group. Exercise is a useful tool for the prevention and regression of atherosclerosis which is evident by our findings of the enhancement of plasma TAC and positive change in serum cholesterol profile. However, the effect of exercise on red cell antioxidant activities is limited in the hypercholesterolemic animals compared to control animals, possibly in part because of alterations in the ability to adapt to exercise-induced oxidative stress in high cholesterol diet.

Key Points

• Plasma MDA, TAC and T-SH concentrations were enhanced by exercise in both control and high cholesterol diet groups.
• GPX activity was significantly reduced in response to exercise in the control group and also in the high cholesterol diet group.
• Eight weeks of chronic exercise reduced atherogenic diet-induced atherosclerotic lesions in all the arteries studied.

Key words: Chronic exercise, antioxidant, malondialdehyde, thiol, atherosclerosis     

Relationship between uremic toxins and oxidative stress in patients with chronic renal failure

OBJECTIVE: Uremic toxins play a critical role in the manifestation of the uremic syndrome. This is a consequence of retention of such substances in chronic renal failure patients and interactions between them. To date >100 uremic compounds have been discovered. The aim of this study was to elucidate potential relationships between N-methyl-2-pyridone-5-carboxamide (Me2PY) and N-methyl-4-pyridone-5-carboxamide (Me4PY), two uremic compounds, and different parameters of oxidative stress. MATERIAL AND METHODS: Forty-three non-dialyzed patients at the Nephrological Outpatients Clinic of Gdansk were enrolled and divided into two groups: (i) 20 patients with a mean estimated glomerular filtration rate (eGFR) of 22.7 ml/min/1.73 m(2); and (ii) 23 patients with a mean eGFR of 12.4 ml/min/1.73 m(2). In both groups, the plasma concentrations of uremic toxins (Me2PY, Me4PY, creatinine), malonyldialdehyde (MDA) and carbonyl groups and the erythrocyte concentration of glutathione (GSH) were analyzed. Correlations between uremic toxins and oxidative stress markers were calculated using Pearson's correlation. RESULTS: We observed significant correlations between serum creatinine and Me2PY (r=0.68; p=0.00001), eGFR and Me2PY (r=-0.55; p=0.00001), Me4PY and serum creatinine (r=0.64, p=0.00001), Me4PY and eGFR (r=-0.59; p=0.00008), MDA and Me2PY (r=0.42; p=0.006), MDA and Me4PY (r=0.38; p=0.02), GSH and Me2PY (r=-0.37; p=0.02) and GSH and Me4PY (r=-0.46; p=0.005), and in particular in patients with severe renal impairment. CONCLUSIONS: We conclude that there is a relationship between the novel uremic toxins described and oxidative stress markers. However, elucidation of the exact pathogenetic links requires further detailed studies.