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1.
De Vega L Férnandez RP Mateo MC Bustamante JB Herrero AM Munguira EB 《Renal failure》2002,24(4):421-432
The aim of this work is to study the temporary variation of oxidative stress in renal transplants, both in plasma and in erythrocytes (CR). In order to do so, we determined total glutathione (GST) levels, both oxidized (GSSG) and reduced (GSH), and the activity of enzymes, glutathione peroxidase (G-px), glutathione reductase (G-red) and glutathione transferase (GSt), in renal transplant patients. Determinations were made 48 h before the transplant 1 week and 2 weeks after the renal transplant. The results obtained confirm 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 is an increase of oxidative stress, which results in an increase of G-red, a marked decrease of G-px in plasma and in erythrocytes (CR) and an abrupt drop both in GST levels in plasma and in GSG (as well as in the [GSH]/[GSSG] relationship). As times goes on, after the transplant, there is a significant improvement in the activity of antioxidant enzymes, but there is no normalization, which is easily seen in the fact that total glutathione levels and the activity of the various enzymes approach the average values of the control group. 相似文献
2.
《Renal failure》2013,35(4):421-432
The aim of this work is to study the temporary variation of oxidative stress in renal transplants, both in plasma and in erythrocytes (CR). In order to do so, we determined total glutathione (GST) levels, both oxidized (GSSG) and reduced (GSH), and the activity of enzymes, glutathione peroxidase (G-px), glutathione reductase (G-red) and glutathione transferase (GSt), in renal transplant patients. Determinations were made 48 h before the transplant 1 week and 2 weeks after the renal transplant. The results obtained confirm 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 is an increase of oxidative stress, which results in an increase of G-red, a marked decrease of G-px in plasma and in erythrocytes (CR) and an abrupt drop both in GST levels in plasma and in GSG (as well as in the [GSH]/[GSSG] relationship). As times goes on, after the transplant, there is a significant improvement in the activity of antioxidant enzymes, but there is no normalization, which is easily seen in the fact that total glutathione levels and the activity of the various enzymes approach the average values of the control group. 相似文献
3.
Oxidative stress markers in pre-uremic patients. 总被引:4,自引:0,他引:4
AIM: The present study was designed to investigate a complex of oxidative stress (OS) markers in patients with chronic renal failure (CRF) and to study the relationship between different OS markers and degree of renal failure. The following indices of OS were measured in plasma: oxidized glutathione (GSSG), reduced glutathione (GSH), total glutathione (TGSH), glutathione redox ratio (GSSG/GSH) and resistance of lipoprotein fraction to oxidation (lag phase of LPF). Baseline diene conjugation level of lipoprotein fraction (BDC-LPF), total antioxidative activity (TAA), diene conjugates (DC), lipid hydroperoxides (LOOH) and thiobarbituric acid-reactive substances (TBARS) were measured in serum. All markers in plasma and serum were measured both in patients with CRF and in healthy controls. SUBJECTS AND METHODS: Blood samples were obtained from 38 patients with CRF and from 61 healthy controls. Routine biochemical analyses were performed by using commercially available kits. RESULTS: Levels of DC, BDC-LPF, LOOH, GSSG and GSSG/GSH ratio were significantly increased and lag phase of LPF was significantly shortened in patients with CRF compared with healthy controls. Serum creatinine and urea levels correlated significantly with GSSG level and GSSG/GSH in patients with CRF. A significant inverse correlation was found between glutathione redox ratio and lag phase of LPF and between GSSG level and BDC-LPF. CONCLUSIONS: The findings suggest that renal patients are in a state of oxidative stress compared with healthy controls. The most informative indices to evaluate the degree of OS in CRF were: GSSG level, GSSG/GSH status, lag phase of LPF and BDC-LPF. 相似文献
4.
Pljesa-Ercegovac M Mimic-Oka J Dragicevic D Savic-Radojevic A Opacic M Pljesa S Radosavljevic R Simic T 《Urologic oncology》2008,26(2):175-181
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. 相似文献
5.
Yi-Chia Huang Shih-Chien Huang Pei-Shan Chung Cheng-Hsu Chen 《Transplantation proceedings》2019,51(8):2667-2670
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. 相似文献
6.
André Renner Martina R Sagstetter Mario E G?tz Volkmar Lange Dominik Bengel Harry Harms Peter Riederer Olaf Elert 《The Journal of heart and lung transplantation》2004,23(9):1093-1102
BACKGROUND: Tissue damage caused by reactive oxygen species (ROS) formed during ischemia/reperfusion seems to be an important risk factor in the failure of transplanted hearts. Although endogenous anti-oxidants protect the myocardium against free radical attack under physiologic conditions, their capacity may become limited during severe oxidative stress. Thus, we investigated the effect of 8-hour cold ischemia on the myocardial anti-oxidative defense system in a heterotopic rat heart transplantation model. METHODS: Lewis rat hearts were subjected to 30 or 480 minutes of 4 degrees C cold ischemia in Bretschneider cardioplegic solution with or without transplantation and reperfusion (30 or 240 minutes) into F344 recipients. Activity levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase (GST), and concentrations of glutathione (GSH), glutathione disulfide (GSSG) and lipid hydroperoxides (LOOH) were analyzed in heart homogenates. For histology, cross-sections of the ventricles were stained with hematoxylin-eosin. RESULTS: Except for GST, enzyme activities and GSSG concentration increased and the glutathione redox ratio (GSH/GSH + 2GSSG) significantly decreased in 480-minute ischemic hearts compared with those with 30-minute ischemia. Reperfusion dramatically decreased both GSH and GSSG and increased LOOH formation but without severe histopathologic findings in the transplants. Applying a tree-structured classifier technique, GSH and LOOH were identified as significant features indicative of transplantation-induced oxidative stress. CONCLUSIONS: In the present study severe loss of glutathione and formation of LOOH indicated transplantation-induced oxidative stress in the rat heart; therefore, alterations of these parameters may hint at relevant deficits in the myocardial anti-oxidative defense and may also predict subsequent tissue damage. 相似文献
7.
Grezzana TJ Corso CO Zanotelli ML Marroni CA Brandão AB Schlindwein E Leipnitz I Meine MH Fleck A Cassal A Hope L Hoppen R Kiss G Gleisner AL Cerski T Bellò-Klein A Severo V Innocenti C Cantisani GP 《Transplantation proceedings》2004,36(4):843-845
BACKGROUND: The mechanisms underlying liver graft dysfunction are not completely defined, although much of the injury derives from oxidative stress in organ reperfusion. The antioxidant glutathione in its reduced form (GSH) is an important agent to detoxify oxygen species after reperfusion. However, this effect might be limited by low concentrations at the end of cold storage. The objective of this study was to evaluate GSH and glutathione oxidized (GSSG) hepatic levels pre- and postreperfusion and correlate with hepatocellular injury and liver function in the 5 subsequent days after transplantation. METHODS: Liver biopsies were taken immediately before implant and 2 hours after venous reperfusion in 34 grafts, determining GSH, GSSG levels, and GSSG/GSH ratio. Aminotransferases (ALT, AST) and PT were measured for 5 days. RESULTS: There was a strong decrease in GSH concentration (P <.0001), increase of GSSG levels (P <.01), and increase of the GSSG/GSH ratio (P <.0001). No correlations were found between GSH, GSSG, or GSH/GSSH levels and AST, ALT, and PT. CONCLUSION: Glutathione levels showed significant changes after 2 hours of reperfusion, due to intense oxidative stress. Therapies to replenish GSH should be considered as a protective measure to avoid liver graft dysfunction after transplantation. 相似文献
8.
Oxidative stress and endothelial function in chronic renal failure. 总被引:19,自引:0,他引:19
M Annuk M Zilmer L Lind T Linde B Fellstr?m 《Journal of the American Society of Nephrology : JASN》2001,12(12):2747-2752
This study aimed to investigate the relationship between oxidative stress and endothelium-dependent vasodilation in patients with chronic renal failure (CRF). Thirty-seven patients with CRF underwent evaluation of endothelium-dependent vasodilation and endothelium-independent vasodilation by means of forearm blood flow measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (evaluating endothelium-dependent vasodilation) and sodium nitroprusside (evaluating endothelium-independent vasodilation). Lag phase of lipoprotein fraction to oxidation, total antioxidative activity, diene conjugates, thiobarbituric acid reactive substances, lipid hydroperoxide, reduced glutathione (GSH), oxidized GSH (GSSG), and the GSH redox ratio (GSSG/GSH) were all measured as markers of oxidative stress. Two groups of healthy subjects (61 and 37 subjects, respectively) were used as controls. In one group, oxidative stress markers were measured, whereas endothelium-dependent vasodilation and endothelium-independent vasodilation were assessed in the other group. Compared with controls, the patients with renal insufficiency had an impaired endothelium-dependent vasodilation, a shorter lag phase of lipoprotein fraction, and higher levels of diene conjugates, lipid hydroperoxide, and GSSG levels. The GSSG/GSH ratio was lower in patients with CRF. Endothelium-dependent vasodilation was positively correlated with total antioxidative activity (r = 0.41, P = 0.016), GSH (r = 0.44, P < 0.0098), and lag phase of LDL (r = 0.35, P = 0.036) and negatively correlated with GSSG (r = -0.40, P < 0.018), GSSG/GSH (r = -0.47, P = 0.0057), and diene conjugates (r = -0.53 P < 0.0015) in patients with CRF. These results show that an impaired endothelium vasodilation function and oxidative stress are related to each other in patients with CRF. 相似文献
9.
Anemia and chronic renal failure: the possible role of the oxidative state of glutathione 总被引:3,自引:0,他引:3
The authors have investigated the oxidative state of glutathione in red blood cells (RBC) and plasma from patients affected by chronic renal failure (CRF) and from age-matched healthy subjects. RBC-reduced glutathione (GSH) levels were significantly lower in CRF patients than in healthy subjects. Oxidized glutathione (GSSG) levels in plasma from CRF patients were higher than in plasma from controls. GSSG levels in RBC were similar in both groups. No differences were noted in GSH plasma levels between patients and controls. The GSSG/GSH ratios in RBC were similar in the two groups; on the contrary, the GSSG/GSH ratio in plasma was significantly higher in CRF patients. High levels of GSSG in plasma could exert two important effects on RBC: (1) inhibition of glucose-6-phosphate dehydrogenase activity, with a consequent alteration of the glutathione system; (2) GSSG easily reacts with hemoglobin to produce hemoglobin-glutathione mixed disulfides, with a consequent protein aggregation and precipitation. In vitro experiments have shown that RBC from CRF patients easily lyse when incubated with their same plasma, but not when incubated in saline buffer. Our results seem to demonstrate that plasma from CRF patients contains various oxidants which could affect the integrity of the glutathione system in RBC. This alteration could play a role in the pathogenesis of anemia in uremic patients. 相似文献
10.
The effect of prostate cancer and antiandrogenic therapy on lipid peroxidation and antioxidant systems 总被引:3,自引:0,他引:3
Iynem AH Alademir AZ Obek C Kural AR Konukoğlu D Akçay T 《International urology and nephrology》2004,36(1):57-62
In living organism, excessive free radicals or oxidative 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. 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 < or = 0.001 and p < or = 0.001 respectively). Plasma MDA level and erythrocyte GST activity of patient group were significantly higher than the levels of control group (p < or = 0.001 and p < or = 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 < or = 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. 相似文献
11.
Domański L Dołgowska B Safranow K Myślak M Rózański J Romanowski M Ostrowski M Domański M Pawlik A Ciechanowski K 《Nephrology (Carlton, Vic.)》2006,11(5):467-470
Background: Generation of reactive oxygen specimens is the basic mechanism leading to ischaemia/reperfusion injury of the kidney graft. Oxygen burst is a trigger for sophisticated biochemical changes leading to generation of oxygenated lipids and changes in microcirculation, which recruit recipient’s neutrophils and contribute to delayed graft function. It has been shown that the free radicals generation correlates with the activity of anti‐oxidative system. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) are involved in protection against free radicals. Aim: To examine the activity of erythrocyte anti‐oxidative system during reperfusion of the transplanted kidney allograft. Methods: The study included 40 renal transplant recipients. Blood was taken from the iliac vein before transplantation and from the graft’s renal vein immediately, as well as 2 and 4 min after total reperfusion. The authors assessed the process of reperfusion using ThermaCAM SC500 termovision camera. Spectrophotometric methods were used to measure superoxide dismutase, glutathione peroxidase and catalase activity as well as glutathione concentrations in erythrocytes. Results: There were no statistically significant differences in the activities of superoxide dismutase, catalase and glutathione peroxidase as well as glutathione concentrations during the first 4 min after total graft reperfusion. Nevertheless, there was a positive correlation between the activity of superoxide dismutase and glutathione peroxidase. Conclusion: The results suggest that the erythrocyte anti‐oxidative system is stable during the early phase after reperfusion. An association between some anti‐oxidative enzymes was noted. 相似文献
12.
Effects of amlodipine and valsartan on oxidative stress and plasma methylarginines in end-stage renal disease patients on hemodialysis 总被引:3,自引:0,他引:3
Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) treatment have a markedly shortened life expectancy in large part owing to cardiovascular disease (CVD), not explained by established risk factors. We tested the hypothesis that therapy with valsartan, an angiotensin receptor blocker and amlodipine, an antioxidant calcium channel blocker will reduce oxidative stress and the plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. We confirmed that compared with age- and gender-matched healthy controls, ESRD patients have excessive oxidative stress and arginine methylation as indexed by elevated plasma levels of oxidation products of lipids (13-hydroxyoctadecadienoic acid (13-HODE)), thiols (oxidized:reduced glutathione, oxidized glutathione (GSSG):GSH), proteins, and nucleic acids, and the methylation products ADMA and symmetric dimethylarginine (SDMA). We undertook a double blind, crossover study of equi-antihypertensive treatment with amlodipine and valsartan for 6 weeks each to test our hypothesis. Both treatments significantly reduced GSSG:GSH, 8-hydroxy 2-deoxyguanosine, ADMA, and SDMA levels and amlodipine reduced 13-HODE. We conclude that hypertensive patients with ESRD receiving HD have evidence of extensive oxidation of lipids, thiols, proteins, and nucleic acids and methylation of arginine that could contribute to CVD. Many of these changes can be reduced by short-term treatment with amlodipine and valsartan. 相似文献
13.
İynem Alkan Hacer Alademir Ayşe Zeynep Öbek Can Kural Ali Riza Konukoglu Dildar Akçay Tülay 《International urology and nephrology》2003,36(1):57-62
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. 相似文献
14.
Renal tubular cell damage and oxidative stress in renal stone patients and the effect of potassium citrate treatment 总被引:8,自引:4,他引:4
Our objective was to evaluate the oxidative stress and renal tubular cell damage in patients who have renal stones compared to normal subjects. The patients were re-evaluated after 1-months supplementation with potassium citrate. We recruited 30 patients (11 males and 19 females) diagnosed with kidney stones and scheduled for surgical stone removal the following month, and 30 healthy non-stone formers (14 males and 16 females). Two 24-h urine samples and one heparinized blood sample were collected from each subject. Plasma was separated from the erythrocytes and assayed for creatinine, potassium, sodium, calcium, magnesium, phosphate, malondialdehyde (MDA, a lipid peroxidation product) (P-MDA), protein thiol as an indicator of protein oxidation, and vitamin E. Erythrocytes were analysed for MDA (E-MDA), reduced glutathione (GSH) and cellular glutathione peroxidase (cGPx) activity. The urine was analyzed for pH, creatinine, potassium, sodium, calcium, magnesium, phosphate, oxalate, citrate, MDA (U-MDA), total protein (U-protein) and N-acetyl--glucosaminidase (NAG) activity. For the stone patients, urine and blood samples were re-evaluated after supplementation with potassium citrate (60 mEq/day) for 1 month. Renal stone patients had higher plasma creatinine and lower plasma potassium, urinary pH, potassium, magnesium, phosphate and citrate than the controls. The patients had higher P-MDA, E-MDA, U-MDA, U-protein and NAG activity, but lower GSH, cGPx activity, protein thiol and vitamin E, when compared with controls. After potassium citrate supplementation, P-MDA and E-MDA decreased while plasma vitamin E, urinary NAG activity and citrate increased. Renal stone disease is associated with high oxidative stress and damage to renal tubular cells. These abnormalities are coincident with an increase in blood lipid peroxidation products and a decrease in antioxidant status. Although supplementation with potassium citrate improved urinary citrate levels and oxidative stress, it neither reduced urinary lipid peroxidation products nor remedied the damage to renal tubular cells, probably due to the existence of kidney stones. 相似文献
15.
Markers of oxidative stress after renal transplantation 总被引:4,自引:0,他引:4
S. Simic-Ogrizovic T. Simic Z. Reljic S. Markovic R. Blagojevic D. Radivojevic V. Lezaic Lj. Djukanovic J. Mimic-Oka 《Transplant international》1998,11(S1):S125-S129
Abstract An increased degree of oxidative stress (OS) in chronic renal failure (CRF) and a possible role of free radicals in CRF have already been described. However, data on OS after renal transplantation are scarce. The aim of the present study was to estimate the degree of OS in renal transplant patients. The study included four groups: 1) 15 haemodialysis patients (HD group), 2) 11 renal transplant patients with stable function (SF group), 3) 12 renal transplant patients with chronic biopsy-proven rejection (CR group), and 4) 10 healthy controls (C group). Markers of OS (malondialdehyde and thiol group levels) and antioxidant activity (glutathione peroxidase and Cu, Zn-su-peroxide dismutase) were determined in plasma and in red blood cells of all examined individuals. After successful renal transplantation a significant improvement, but not normalization, of antioxidant enzyme activities accompanied by significantly reduced lipid peroxidation were found. In the CR group the degree of OS was increased, and our results suggest that OS may be a relevant pathophysiological factor for CR development. 相似文献
16.
Reperfusion injury of the liver: role of mitochondria and protection by glutathione ester. 总被引:7,自引:0,他引:7
BACKGROUND: Reperfusion injury of the liver is characterized by intravascular oxidative stress and GSH consumption. Whether mitochondria contribute to hepatocellular damage has never been elucidated. Therefore, we assessed mitochondrial function and redox state during reperfusion and the effect of glutathione monoethyl ester (GSHE) administration, which may replenish the GSH pool. MATERIALS AND METHODS: Rats were subjected to partial hepatic ischemia (90 min) followed by reperfusion. Mitochondrial function was assessed in vivo and in vitro by the KICA breath test and the ATP synthase activity. Just prior to the start of reperfusion, rats received 5 mmol/kg of GSHE or saline iv. ALT, total and oxidized (GSSG) glutathione, GSHE, and CYS were measured in plasma and liver. GSH, GSSG, malondialdehyde (MDA), and carbonyl proteins were measured in mitochondria. The extent of necrosis was also estimated. Sham-operated rats served as controls. RESULTS: Reperfusion markedly increased ALT (>1500 U/L) and doubled the liver content of MDA and carbonyl proteins. Mitochondrial GSH decreased approximately 30%, without increase of GSSG. The in vivo KICA breath test was not significantly impaired by reperfusion. In contrast, both KICA decarboxylation and ATP synthase activity were both reduced by approximately 50% in mitochondria isolated from reperfused livers. GSHE administration significantly decreased ALT ( approximately 40%), protected ATP synthase activity, and reduced the extent of necrosis. Compared to controls, plasma GSHE and plasma GSH at 1 h were lower in rats subjected to ischemia. GSHE was higher in reperfused lobes than in continuously perfused ones and the concentration of GSH was significantly higher in ischemic liver than in untreated animals, indicating that the uptake of GSHE is increased in postischemic liver. GSHE prevented the reperfusion-associated increase of oxidized products in liver and mitochondria. CONCLUSIONS: Reperfusion of ischemic liver is associated with oxidative modifications and functional impairment of mitochondria. GSHE protects against reperfusion injury, possibly by providing intra- and extracellular GSH. 相似文献
17.
Pawan Kumar Verma Rajinder Raina Mudasir Sultana Maninder Singh Pawan Kumar 《Renal failure》2016,38(1):142-150
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?0.05) the levels of blood urea nitrogen, creatinine (CR), TOS, OSI and malondialdehyde (MDA) but lowered (p?0.05) total plasma proteins, TAS, total thiols (TTH), blood glutathione (GSH) and antioxidant enzymes compared to the control group. Pre- and post-treatments of ethanolic floral extract of 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?0.05) MDA level in renal tissue without restoring the erythrocyte MDA level following cDDP treatment. These observations were further supported by the histopathological findings in renal tissue. Observations of the present study have shown that treatments with ethanolic floral extract of C. officinalis protect cDDP induced nephrotoxicity by restoring antioxidant system of the renal tissue. 相似文献
18.
Pretreatment of animals with certain antioxidant enzymes and substances decreases renal damage following ischemia and reperfusion. The hypothesis that reoxygenation imposes an oxidant stress has been used to explain this. The present study has directly assessed oxidant stress under these conditions by measuring the glutathione redox ratio ([GSSG/(GSH + GSSG)] x 100) in freeze-clamped kidney. The glutathione peroxidase system plays a role in removing peroxides which result from oxidant stress, generating GSSG from GSH in the process. The selenium-dependent glutathione peroxidase can metabolize H2O2 and other hydroperoxides. A non-selenium-dependent glutathione peroxidase activity is present and can metabolize organic hydroperoxides, but it cannot metabolize H2O2. Under anesthesia, the left renal artery was occluded for 40 minutes and then reflow was allowed. Kidneys were freeze clamped before reflow and after 5, 10, and 15 minutes of reflow. The contralateral kidney was freeze clamped and used as a control. The control value for the glutathione redox ratio was 1.09 +/- 0.05. This fell during ischemia to 0.67 +/- 0.22 and increased significantly to 1.66 +/- 0.29 after five minutes of reperfusion. By 15 minutes it had returned to 1.09 +/- 0.22. Treatment of rats with diquat, which causes a severe oxidant stress, raised the glutathione redox ratio from 0.88 +/- 0.12 to 1.89 +/- 0.15. Thus, reperfusion was concluded to cause a large but transient oxidant stress. Selenium-deficient rats were used to examine the nature of the oxidant stress. Activity of the selenoenzyme glutathione peroxidase was depressed to 2% of control in the kidneys of these rats.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
19.
A time course of contusion-induced oxidative stress and synaptic proteins in cortex in a rat model of TBI 总被引:1,自引:0,他引:1
An imbalance between oxidants and antioxidants has been postulated to lead to oxidative damage in traumatic brain injury (TBI). Oxidative neurodegeneration is a key mediator of exacerbated morphological responses and deficits in behavioral recoveries. The present study was designed to delineate the early temporal sequence of this imbalance in order to enhance possible antioxidant therapy. Young adult male Sprague-Dawley rats were subjected to a unilateral moderate cortical contusion. At various times post-trauma (3, 6, 12, 24, 48, 72, and 96 h), animals were killed and the cortex analyzed for enzymatic and non-enzymatic oxidative stress markers. Fresh tissues were prepared for biochemical analysis of several antioxidants (glutathione [GSH], glutathione peroxidase [GPx], glutathione reductase [GR], glutathione-S-transferase [GST], and thiobarbituric acid reactive substances [TBARS]). Synaptic markers Synapsin-I, PSD-95, SAP-97 and GAP-43 were analyzed by Western blot with antibodies directed against them. All activity levels were compared to sham-operated animals. Activity of antioxidant enzymes and GSH clearly demonstrate a significant time-dependent increase in oxidative stress. Changes in pre- and post-synaptic proteins (Synapsin-I and PSD-95) occur early (24 h), whereas SAP-97 levels demonstrate a protracted reduction. These results indicate that depletion of antioxidant systems following trauma could adversely affect synaptic function and plasticity. Because of the observed differences in the time-course of various markers, it may be necessary to stagger selective types of anti-oxidant therapy to target specific oxidative components. The initial therapeutic window following TBI appears relatively short since oxidative damage occurs as early as 3 h. 相似文献
20.
Kuchta A Pacanis A Kortas-Stempak B Cwiklińska A Ziętkiewicz M Renke M Rutkowski B 《Kidney & blood pressure research》2011,34(1):12-19
Changes mediated by oxidative stress are thought to be involved with atherosclerosis in patients with chronic kidney disease (CKD). The purpose of this study was to analyze the markers of oxidative damage and the activity of antioxidative enzymes as well as the total antioxidant capability in patients with different stages of CKD, both conventionally treated and dialyzed. We evaluated the oxidative modification of lipids (by oxidized low-density lipoprotein and malonodialdehyde levels) and proteins (by advanced oxidation protein products level). We also assessed the activity of paraoxonase-1 and glutathione peroxidases and total antioxidant status. Compared with the control group, the uremic patients, both dialyzed and nondialyzed, had higher levels of all studied plasma oxidative stress markers and decreased activity of antioxidative enzymes. Our results lead us to conclude that oxidative stress seems to be related rather to the uremic state than to the dialysis treatment. We also showed that estimating total antioxidant status in a simple test is unreliable for assessing the antioxidant ability of patients with CKD. 相似文献