The effect of prostate cancer and antianrogenic therapy on lipid peroxidation and antioxidant systems

In living organism, excessive free radicals oroxidative damage which occur as a result of deficient antioxidant defensive mechanisms by the effect of endogenous and exogenous factors, influences especially developmental steps of chemically induced cancers [1, 2]. In our study, plasma malondialdehyde level (MDA) as an indicator of lipid peroxidation, erythrocyte glutathione (GSH) level as an indicator of antioxidant state, glutathione reductase (GSH-Red), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) as an antioxidant enzymes and plasma vitamin E level were detected in patients with prostate cancer (21 males; age, 69.4 ± 4.8 years) before and after three months of antiandrogenic therapy with goserelin acetate as luteinizing hormone releasing hormone (LHRH) analogue. Healthy people evaluated as a control group (20 males; age, 63.7 ± 3.9). Erythrocyte GSH levels, the activities of GSH-Red and GSH-Px and plasma vitamin E levels were found significantly low in patients with prostate cancer when compared with the healthy subjects (p < 0.01, p < 0.05, p ≤ 0.001 and p ≤ 0.001 respectively). Plasma MDA level and erythrocyte GST activity of patient group were significantly higher than the levels of control group (p ≤ 0.001 and p ≤ 0.001 respectively). After antiandrogenic therapy erythrocyte GSH level, GSH-Red, GSH-Px activity and plasma vitamin E level were found unchanged. Significant decrease in plasma MDA level and significant increase in erythrocyte GST activity were detected in patient group (p < 0.05 and p ≤ 0.01 respectively). The study has revealed the shift in the oxidant-antioxidant balance towards oxidative state in patients with metastatic prostate cancer. Our results showed that antiandrogenic therapy increased in GST activity, decreased in lipid peroxidation. This revised version was published online in August 2006 with corrections to the Cover Date.     

The levels of glutathione peroxidase, vitamin A, E, C and lipid peroxidation in patients with transitional cell carcinoma of the bladder

OBJECTIVE: To assess the levels of erythrocyte glutathione peroxidase (GSH-Px), and the serum levels of antioxidant vitamins (A, E and C), selenium and malondialdehyde (MDA) in patients with transitional cell carcinoma (TCC) of the bladder. PATIENTS, SUBJECTS AND METHODS: The study comprised 91 people (23 healthy controls and 68 patients with TCC). Erythrocyte GSH-Px activity was measured by spectrophotometry, high-performance liquid chromatography to detect serum levels of vitamins and MDA, and fluorometry to detect serum levels of selenium. RESULTS: The serum levels of vitamin A, E and C, and selenium were significantly lower (P < 0.05) in patients with TCC than in controls. However, erythrocyte GSH-Px activities (P < 0.05) and serum MDA levels (P < 0.01) were significantly higher in patients with TCC than in the controls. CONCLUSIONS: Levels of free oxygen species were higher, and antioxidant vitamin and selenium levels lower, in patients with bladder TCC than in controls. These findings, with the results of previous animal studies, suggest that giving vitamin A, C, E and selenium may be beneficial in preventing and treating human bladder cancer.     

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。     

Plasma Homocysteine and Glutathione Are Independently Associated With Estimated Glomerular Filtration Rates in Patients With Renal Transplants

BackgroundElevated levels of plasma homocysteine could, through homocysteine oxidation, induce the overproduction of reactive oxygen species, leading to a reduction in glutathione-related antioxidants, and may impair graft functions in patients with renal transplants. The purpose of this study was to determine whether plasma homocysteine, glutathione, or its related antioxidants were related to graft functions in patients with renal transplants.Patients and MethodsWe recruited 66 patients (mean age 48.4 years) with renal transplants (mean transplant duration 8.3 years). Patients were divided into 2 groups, based on their estimated glomerular filtration rate (eGFR): the moderate graft function group (eGFR ≥ 60 mL/min/1.73 m², n = 37) and low graft function group (eGFR < 60 mL/min/1.73 m², n = 29). We then determined their fasting levels of the following: malondialdehyde (MDA), homocysteine, cysteine, pyridoxal 5′-phosphate (PLP), glutathione (GSH), oxidized glutathione (GSSG), GSH/GSH ratio, glutathione peroxidase (GSH-Px) activity.ResultsWe found in the low graft function group significantly higher levels of plasma homocysteine, cysteine, GSH, and GSH/GSSG ratios. But an intergroup difference was not found regarding levels of MDA, PLP, GSSG, and GSH-Px activity. After adjusting for potential confounders, the increased plasma homocysteine and GSH levels were independently associated with lower eGFR. No interaction existed between homocysteine and GSH levels in association with eGFR.ConclusionIncreased plasma homocysteine and GSH levels appeared to be independent indicators of decreased graft functions in patients with renal transplants.     

Altered antioxidant capacity in human renal cell carcinoma: role of glutathione associated enzymes

PURPOSE: We aimed to discern the role of glutathione (GSH) associated enzymes in maintaining high GSH levels in renal cell carcinoma (RCC) of the clear cell type and analyze RCC enzyme antioxidant capacity. Since changes in cellular redox balance in RCC might also be related to alterations of glutathione S-transferase (GST) phenotype, GST class alpha and pi expression was also explored. METHODS AND MATERIALS: Human kidney specimens of tumor and distant nontumor regions were obtained from 15 patients with RCC at the time of surgery. The activities of GSH-replenishing enzymes, gamma-glutamylcysteine synthetase (gamma-GCS), gamma-glutamyl transferase (gamma-GT), and glutathione reductase (GR), as well as the activities of antioxidant enzymes glutathione peroxidase (GPX) and catalase (CAT) were determined spectrophotometrically. GST alpha and pi class expression was determined by immunoblot. RESULTS: In the course of renal cancerization, significant changes appear in the activities of GSH-replenishing and antioxidant enzymes. The activity of the key enzyme of GSH synthesis, gamma-GCS, is up-regulated (P < 0.001), while the activities of gamma-GT and GR are down-regulated in renal tumors compared to nontumor tissue (P < 0.001 and P < 0.05, respectively). Activities of GPX and CAT were also down-regulated (P < 0.001 and P < 0.05, respectively) in RCC. Changes in enzyme antioxidant capacity in RCC were associated with decreased GST class alpha (P < 0.001) and unchanged GST pi expression at the protein level. CONCLUSIONS: Changes in redox status in RCC as a consequence of decreased enzyme antioxidant capacity, together with altered GST alpha expression, may be important factors in development and tumor growth. The up-regulation of gamma-GCS and high levels of GSH in RCC may be an attempt to limit injury caused by oxidative stress.     

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.     

Haemolysis in haemodialysis patients: evidence for impaired defence mechanisms against oxidative stress.

BACKGROUND: Uraemic patients have a decreased ability to withstand oxidative stress. It is postulated that their antioxidant capacity is reduced, yet the mechanism remains unclear. Recently 33 haemodialysis (HD) patients were exposed to chloramine contamination in the water supply. This led to haemolysis in 24 patients, while nine were unaffected. In the former group haemoglobin decreased from 11.7+/-1.1 to 8.5+/- 1.4 g/dl (P<0.0001) and returned to 11.4+/-0.9 g/dl (P<0.0001) following recovery. During haemolysis, haptoglobin was 38.4+/-10.6 vs 138.1+/-8.3 ng/dl (P<0.0001) following recovery. METHODS: To explore the factors affecting the severity of haemolysis we studied extracellular and intracellular anti-oxidant defence mechanisms 3 months after recovery. In 29 patients and 20 controls we determined plasma glutathione (GSH), and the erythrocyte enzymes glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rx), and superoxide dismutase (SOD). Serum malondialdehyde (MDA) was measured as a marker of oxidative stress. RESULTS: Plasma GSH was lower in patients as compared to controls (5.49+/-0.26 vs 7.4+/-0.5 micromol/l, P<0.005). There was an inverse correlation between GSH and the degree of haemolysis (r=-0.42, P<0.02). Patients had higher GSH-Rx (4.64+/-0.15 vs 3.97+/-0.12 U/gHb, P<0.02), lower GSH-Px (29. 7+/-1.85 vs 35.5+/-1.62 U/gHb, P<0.001), and similar SOD (0.63+/-0. 02 vs 0.51+/-0.02 U/mgHb) as compared to controls. There was no correlation between the enzyme levels and the degree of haemolysis. MDA was higher in patients (2.37+/-0.07 vs 0.97+/-0.1 nmol/ml, P<0. 0001). There was a correlation between MDA and the years patients were on HD (r=0.43, P<0.02). CONCLUSIONS: These data indicate that HD patients have an impaired anti-oxidant response, which may be attributed in part, to plasma GSH deficiency. Patients with the lowest plasma GSH levels are more susceptible to oxidative stress and consequent haemolysis.     

Study of the activity of glutathione-peroxidase,glutathione-transferase,and glutathione-reductase in renal transplants

The aim of this work was to study the temporare variation of oxidative stress in the plasma and erythrocytes (CR) of renal transplant patients We determined total glutathione (GST), as well as oxidized (GSSG) and reduced (GSH) fractions and the activity of glutathione peroxidase (G-px), glutathione reductase (G-red) and glutathione transferase (GSt). Determinations were performed 48 hours before transplant as well as 1 and 2 weeks after the renal transplant. The results showed a high "oxidative stress" rate, resulting from the equilibrium between the production of free radicals and the activity of antioxidants, the former being higher proportionally. Immediately after the transplant, there was an increase in oxidative stress, which resulted in an increased G-red, a marked decrease in plasma and in erythrocyte G-px (CR9 and an abrupt drop both in GST levels in plasma and in GSG (as well as in the [GSH]/[GSSG] relationship). Thereafter there was a significant improvement in the activity of antioxidant enzymes, but without normalization; the total glutathione levels and the activity of various enzymes approached the average values of the control group.     

Antioxidative status and lipid peroxidation in kidney tissue of rats fed with vitamin B6-deficient diet

Introduction: The aim of this study was to evaluate lipid peroxidation (LP) and free radical scavenging enzyme activities in kidney tissue of vitamin B₆-deficient rats. Material and Methods: The rats were divided into control and vitamin B₆-deficient groups. After 4 weeks of feeding, animals in all groups were anesthetized by thiopental sodium (50 mg/kg). Thoraces were opened, 2 mL blood samples were taken from aortas, then the rats were killed by cervical dislocation, and kidney tissues were removed. Biochemical measurements in kidney tissue were carried out using a spectrophotometer. Results: Total superoxide scavenger activity (TSSA), nonenzymatic superoxide scavenger activity (NSSA), superoxide dismutase (SOD) activities, and antioxidant potential (AOP) values in the vitamin B₆-deficient group were significantly lower than those of the control group, whereas glutathione peroxidase (GSH-Px), glutathione reductase (GRD), glutathione-S-transferase (GST) activities, and malondialdehyde (MDA) level were significantly higher than those of the control group (p < 0.05). Discussion: The results show that vitamin B₆ deficiency causes an attenuation in antioxidant defense system and an increase in oxidative stress in kidney tissue of rats.     

Roles of paraoxonase and oxidative stress in adolescents with uraemic, essential or obesity-induced hypertension

BACKGROUND/AIMS: Paraoxonase 1 (PON1) is associated with high-density lipoproteins in the plasma, and is capable of hydrolysing oxidized lipids and preventing the oxidation of low-density lipoproteins. Oxidative stress and the PON1 (activity and Q192R polymorphism) were analysed in adolescent patients with essential (n = 49) or obesity-induced hypertension (n = 79), uraemic patients (n = 20), and also in obese normotensive patients (n = 60) and age-matched controls (n = 57). METHODS: The PON1 activity was measured via paraoxon hydrolysis. The PON1 genotype was determined by real-time PCR. The levels of oxidized and reduced glutathione, the end-products of nitric oxide, cysteine, homocysteine and lipid peroxidation in the plasma were measured and related to the PON1 status. RESULTS: There were no significant differences between the patient groups and the control group in the genotype distributions and the allele frequencies of the Q192R polymorphism. The PON activity was significantly lower (p < 0.001) in the uraemic hypertensive group than in the controls. The MDA concentration was significantly higher in the uraemic hypertensive (p < 0.001) and obese hypertensive (p < 0.05) patients. The plasma NOx concentrations were significantly lower (p < 0.001) and the ratio MDA/NOx were significantly higher in all four patient groups. The GSH levels were significantly lower in the patients with hypertension (p < 0.001) and obesity-induced hypertension (p < 0.05) than in the controls, while the GSSG level (p < 0.01) and the ratio GSSG/GSH (p < 0.05) was significantly higher in the uraemic hypertensive group. The plasma homocysteine level was significantly higher (p < 0.001) in the uraemic hypertensive patients as compared with the controls. CONCLUSIONS: We found no significant correlation between the biochemical parameters and neither genotypes nor enzyme activities. The PON1 status and the levels of certain biochemical parameters are independently associated with the hypertension in hypertensive and obese hypertensive patients, and the elevated levels of lipid peroxides and plasma homocysteine may contribute to the increased risk of cardiovascular complications in patients on haemodialysis.     

Lipid peroxidation and antioxidant enzymes in children on maintenance dialysis

End-stage renal disease (ESRD) is associated with numerous complications, which may partly result from excessive amounts of reactive oxygen species and/or decreased antioxidant activity. The aim of the study was to evaluate lipid peroxidation (LP) in plasma and erythrocytes, erythrocyte antioxidant enzyme activity (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GSH-Px), and concentrations of Cu and Zn as cofactors of SOD and Se as a cofactor of GSH-Px in erythrocytes, plasma and in dialysis fluid in children with ESRD. In particular, we analyzed whether the modality of dialysis could modify oxidative stress parameters in children. To determine the influence of hemodialysis (HD) on oxidative stress, the measurements were also performed on HD children 20 min after the beginning of the dialysis session. Thirty-one patients participated in the study: group I with 10 children on continuous ambulatory peritoneal dialysis (CAPD), and group II with 21 on HD. The erythrocyte malondialdehyde concentrations (E-MDA), plasma MDA (P-MDA) and plasma organic hydroperoxide (OHP) in children from both groups were higher than in controls. E-MDA and P-MDA in HD before the session was lower compared to the values after 20 min of HD session (time T²⁰). The activity of SOD, GSH-Px, CAT, concentrations of erythrocyte and plasma Se, Cu, Zn were lower in children with ESRD than in controls. In the HD group, the activity of GSH-Px, CAT, and levels of trace elements in erythrocytes and in plasma were diminished at time T²⁰. In conclusion, increased oxidative stress occurs in children on maintenance dialysis, independent of dialysis modality. The activity of the enzymatic antioxidant defence system is highly reduced in red blood cells of pediatric dialysis patients. Children with ESRD exhibit lower trace element (Se, Cu, Zn) levels in plasma and erythrocytes as compared to healthy subjects. Oxidative stress is aggravated during every single HD session in children.     

Centella asiatica alleviates diabetes-induced changes in fatty acid profile and oxidative damage in rat testis

The in vivo effects of Centella asiatica L. Urban (Family: Apiaceae; CA) on diabetes-induced testicular fatty acid misdistribution and oxidative injury were investigated. Diabetic rats were treated with vehicle, CA or metformin daily for 14 days by oral gavage. Fatty acid (FA) content in testis was analysed using gas chromatography-flame ionisation detection while redox indices were measured as peroxide value (PV), malondialdehyde (MDA), oxygen radical antioxidant capacity (ORAC), reduced glutathione (GSH), glutathione S-transferase (GST) and glutathione peroxidase (GPx) activities. Diabetes increased omega-6 (61%), and decreased omega-3 (23%) and monounsaturated fatty acids (MUFA; 18%) compared to non-diabetic controls. Oxidative injury in diabetic rats was confirmed by increases in PV (112%) and MDA (77%) in addition to decreases in GSH (41%) and activities of GST (19%) & GPx (24%) compared to non-diabetic controls. CA treatment led to 17% reduction in omega-6 and 33% rise in MUFA compared to diabetic controls. Additionally, CA ameliorated the oxidative injury and improved antioxidant capacity by increasing GSH (49%), GST (16%) and GPx (23%) when compared to diabetic controls. Data suggest CA potential in alleviating the alterations caused by diabetes in testes through effects on omega-6 and MUFA; and via increased GSH level and dependent enzyme activities.     

Low hair selenium and plasma glutathione peroxidase in children with chronic renal failure

Selenium (Se) is a trace element that incorporates into the selenoenzyme glutathione peroxidase (GSH-Px). There are conflicting results regarding the Se levels and activity of GSH-Px in adult uremic patients. The aim of this study was to determine (1) the hair Se status, (2) the possible relation between the hair Se status and the antioxidant enzyme, GSH-Px, and (3) the influence of different treatment procedures on hair Se status and GSH-Px activity in children with CRI, those treated conservatively and those on HD and on CAPD. Ninety-three patients, including 32 patients with CRI, treated conservatively, 42 PD patients, 19 HD patients and 34 healthy children were enrolled in the study. The hair Se level was measured by the atomic absorption spectrophotometer method. Plasma GSH-Px activity was determined using a Randox test combination (RANSEL). Hair Se levels were significantly lower in the CRI, CAPD, and HD groups when compared to the control group (P=0.001, P=0.001, and P=0.001, respectively). Plasma GSH-Px activity was significantly lower in the CRI, CAPD, and HD groups when compared to the control group (P=0.001, P=0.001, and P=0.001, respectively). Plasma GSH-Px activity correlated with the GFR in patients with CRI and the control group (P=0.000; r²=0.60). There was no correlation between plasma GSH-Px and hair Se levels in the patient and control groups. These results revealed a decreased hair Se level and impaired antioxidative capacity in children with CRI on CAPD and HD. The lack of any relation between plasma GSH-Px and hair Se suggests that plasma GSH-Px is not a good marker of Se stores.     

Antioxidant status of children with steroid-sensitive nephrotic syndrome

Eighteen children with steroid-sensitive nephrotic syndrome (SSNS) were studied. The control group comprised 20 healthy children. The following indirect parameters of reactive oxygen species activity were determined in nephrotic patients during four stages of the disease (full relapse before prednisone administration, disappearance of proteinuria, prednisone cessation, unmaintained remission): plasma malondialdehyde (MDA) levels, copper/zinc superoxide dismutase (CuZn SOD) activity and glutathione peroxidase (GPX) activity in erythrocytes, reduced glutathione (GSH) and vitamin C levels in whole blood, and vitamin E level in serum. Increased MDA levels, reduced vitamin C levels, and enhanced CuZn SOD activity were found in relapse. GSH concentration was high during all four stages. Vitamin E level was also increased, parallel to the pattern of serum lipids. GPX activity remained low during the proteinuria stage and in remission. We conclude that the majority of abnormal findings can be attributed to the hyperlipidemia of NS. Low GPX activity may be a factor limiting the antioxidant capacity in NS. The present study is inconclusive regarding the role of free radicals in the proteinuria of NS. Received October 13, 1997; received in revised form April 13, 1998; accepted April 14, 1998     

Impairment of glutathione biosynthetic pathway in uraemia and dialysis.

BACKGROUND: Glutathione (GSH), the predominant intracellular antioxidant, reportedly has been shown to be decreased in chronic renal failure patients, which renders these patients more susceptible to oxidative damage by free radicals. To our knowledge, the ability of erythrocytes to normalize the GSH level by de novo synthesis in uraemic and dialysis patients has not been studied previously. The main goal of the present study was to measure the activities of the enzymes that are responsible for de novo GSH generation, namely gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase (GSH-S), in erythrocytes from uraemic and dialysis patients. METHODS: Erythrocyte total GSH level and gamma-GCS and GSH-S activities as well as plasma malondialdehyde (MDA) levels were measured in 19 non-dialysis patients (ND), 34 haemodialysis patients (HD), 22 continuous ambulatory peritoneal dialysis patients (CAPD) and 21 normal healthy controls. The effect of a single haemodialysis session was determined in 16 HD patients. RESULTS: Significant decreases in GSH levels and gamma-GCS activity but not GSH-S were observed in ND, HD and CAPD patients compared with controls. However, GSH levels as well as gamma-GCS and GSH-S activities were not different among the ND, HD and CAPD patients. The decrease in GSH was strongly and positively correlated with the decrease in gamma-GCS in ND, HD and CAPD patients (r = 0.717, P<0.001; r = 0.854, P<0.001; and r = 0.603, P<0.01, respectively). In addition, plasma MDA was negatively correlated with gamma-GCS in ND, HD and CAPD patients (r = 0.721, P<0.001; r = 0.560, P<0.01; and r = 0.585, P<0.01, respectively). A single dialysis session had no effect on GSH level or on gamma-GCS and GSH-S activities. Only a significant reduction in MDA was observed at the end of dialysis. CONCLUSIONS: The activity of the rate-limiting enzyme in GSH biosynthesis, gamma-GCS, was significantly decreased in uraemic and dialysis patients, which explains, at least in part, frequent reports of reduced GSH levels in these patients. The decrease in gamma-GCS activity may have been secondary to inhibitory effects from uraemic factors that are not removed by standard dialysis. However, this assumption does not exclude the possibility of down-regulation of gamma-GCS protein expression and further studies in this context are recommended.     

Effect of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on peritoneal dialysis and hemodialysis

BACKGROUND: Several medications have been tested with the aim of decreasing oxidative stress and erythrocyte osmotic fragility in patients on dialysis. The aim of the present study was to assess the influence of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on hemodialysis (HD) and peritoneal dialysis (PD). METHODS: This was a placebo-controlled study. The study was performed on 34 HD patients, 13 PD patients and 22 healthy volunteers with a mean age of 45.57 +/- 8.54 years. HD patients were divided into 2 groups: treatment (n=19) and control (n=15). Vitamin E was administered, 300 mg/day, to the HD treatment group and PD patients for 20 weeks. Lipid peroxidation, antioxidant condition and erythrocyte osmotic fragility (EOF) were examined before and after treatment. RESULTS: Before the treatment, the levels of EOF (p<0.001) and malondialdehyde (MDA) (p<0.001) were significantly lower, and erythrocyte superoxide dismutase (SOD) (p=0.001) and vitamin E levels (p<0.001) were significantly higher in the healthy group than PD and HD groups. Serum vitamin E increased from 0.93 +/- 0.16 to 1.09 +/- 0.14 mg/dL (p=0.001), EOF decreased from 0.49% +/- 0.03% to 0.42% +/- 0.04% NaCl (p<0.001), and plasma MDA values decreased from 2.77 +/- 0.87 to 2.20 +/- 0.767 nmol/mL (p=0.018) in the HD treatment group after vitamin E treatment. Levels of EOF decreased from 0.51% +/- 0.09% to 0.43% +/- 0.03% NaCl in the PD treatment group after vitamin E treatment (p=0.021). CONCLUSION: Vitamin E therapy is effective in decreasing the levels of EOF in patients on HD and PD, and it is also effective in decreasing lipid peroxidation in patients on HD.     

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.     

Alteration in plasma antioxidant capacity in various degrees of chronic renal failure

AIM, PATIENTS AND METHODS: To obtain a more comprehensive profile of extracellular antioxidant capacity in chronic renal failure (CRF), markers of oxidative stress (malondialdehyde, MDA and hydrogen peroxide), protein SH groups (as an important chain-breaking antioxidant) and activity of antioxidant enzymes (glutathione peroxidase, [GPX], catalase and superoxide dismutase, [SOD]) were studied in plasma of 36 non-dialyzed patients with various degrees of CRF and 10 hemodialyzed (HD) patients. RESULTS: The results show that plasma MDA concentrations significantly increase with the severity of kidney dysfunction (r = -0.543, p < 0.01). A marked and profound fall in plasma thiol group levels was observed in all groups tested, independent of the degree of renal failure (r = 0.082, p > 0.05). Plasma SOD activity increased in CRF patients with the progression of renal insufficiency (r = -0.370, p < 0.05). On the other hand, plasma GPX activity decreased progressively in strong correlation with endogenous CCr (r = 0.712, p < 0.001). However, despite this imbalance between extracellular SOD and GPX activities, plasma concentration of hydrogen peroxide remained unchanged in non-dialyzed CRF patients. Catalase activity in non-dialyzed CRF patients was increased, suggesting the significant involvement of catalase in the regulation of plasma hydrogen peroxide level. CONCLUSION: In hemodialyzed patients significantly lower plasma catalase activity, associated with higher hydrogen peroxide levels, was found. It seems reasonable to assume that the imbalance in the activity of extracellular antioxidant enzymes in chronic renal failure may result in accumulation of free radical species, and in unscheduled oxidation of susceptible molecules.     

Correlation of plasma and tissue oxidative stresses in intra-abdominal sepsis

BACKGROUND: The aim of this study was to investigate the correlation between plasma and tissue oxidative stress and the antioxidative response, by measuring malon dialdehyde (MDA) and glutathione (GSH) in late sepsis induced by cecal ligation and perforation. MATERIALS AND METHODS: A prospective, randomized, controlled experimental study in rats was done. Forty rats, weighing 200-250 g, were randomly divided into two groups (n = 20). In group 1, laparotomy was performed under aseptic conditions, and the cecum ligated and perforated. The abdomen was closed. In group 2, sham control, there was only laparotomy. Twenty-four hours later, blood samples were taken by cardiac puncture for plasma MDA and GSH, followed by harvesting of samples from lung, liver, kidney, and heart in both groups. RESULTS: In the liver, lung, plasma, heart, and kidney, MDA concentrations were increased in the sepsis group after 24 h (P < 0.001 for all organ samples). In the same organs, GSH concentrations were decreased by sepsis (P < 0.001 for all organ samples). In both groups, plasma MDA was positively correlated to MDA in heart (r = 0.82, P < 0.001), liver (r = 0.76, P < 0.001), lung (r = 0.78, P < 0.001), and kidney (r = 0.73, P < 0.001). Similarly, plasma GSH was positively correlated to GSH in liver (r = 0.93, P < 0.001), heart (r = 0.86, P < 0.001), lung (r = 0.91, P < 0.001), and kidney (r = 0.79, P < 0.001). CONCLUSIONS: Plasma MDA and GSH were positively correlated with tissue MDA and GSH in intra-abdominal sepsis in a rat model.     

Total antioxidant and oxidant status of plasma and renal tissue of cisplatin-induced nephrotoxic rats: protection by floral extracts of Calendula officinalis Linn.

The present study was aimed to determine the total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) of plasma and renal tissue in cisplatin (cDDP) induced nephrotoxic rats and its protection by treatments with floral extracts of Calendula officinalis Linn. Treatment with cDDP elevated (p?p?C. officinalis along with cDDP restored (p?>?0.05) CR, albumin, TOS, GSH and activities of antioxidant enzymes in blood and renal tissue. Ethanolic extract treatments reduced (p?C. officinalis protect cDDP induced nephrotoxicity by restoring antioxidant system of the renal tissue.