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1.
Atherosclerosis development is accelerated in chronic renal failure (CRF) and is the major cause of death in this clinical condition. An increased oxidative stress and an endothelial dysfunction, with their complex interrelationships, are relevant aspects of atherogenesis in CRF patients and might be targets for treatment. Many studies have underlined the cardiovascular protection provided by a moderate wine consumption. This beneficial effect is due to both alcohol and nonalcoholic components of wine including several phenolic molecules such as quercetin and resveratrol. Wine polyphenols have antioxidant properties and favorably influence endothelial function, in particular by stimulating nitric oxide-mediated vasodilation and inhibiting the endothelin-1 pathway. The possible advantage of a moderate wine consumption in CRF patients can be hypothesized and deserves clinical investigation. 相似文献
2.
Endothelial dysfunction in chronic renal failure: roles of lipoprotein oxidation and pro-inflammatory cytokines. 总被引:17,自引:4,他引:13
C H Bolton L G Downs J G Victory J F Dwight C R Tomson M I Mackness J H Pinkney 《Nephrology, dialysis, transplantation》2001,16(6):1189-1197
BACKGROUND: Chronic renal failure (CRF) is associated with an increased risk of ischaemic heart disease (IHD), but the mechanisms responsible are controversial. We investigated the relationship of two sets of candidate mechanisms-indices of LDL oxidation and markers of inflammatory activity-with vascular endothelial dysfunction (VED). METHODS: We carried out cross-sectional analysis of 23 dialysed and 16 non-dialysed CRF patients, 28 healthy controls, and 20 patients with stable angina and normal renal function. The following were determined: (i) LDL oxidation by Cu(2+) and ultraviolet light, serum autoantibodies to oxidized LDL (oxLDL); (ii) forearm flow-mediated vasodilatation, plasma concentrations of adhesion molecules, and von Willebrand factor (vWF); and (iii) circulating levels of TNF-alpha and IL-6, C-reactive protein (CRP), and fibrinogen. RESULTS: Endothelium-dependent vasodilatation (EDV) was lower in angina, pre-dialysis, and dialysis CRF patients than in controls (all P<0.005). Compared with controls, vWf (P<0.005) and adhesion molecules (vCAM-1, P<0.005; iCAM-1, P=0.01; E-selectin, P=0.05) were raised in dialysis, and vCAM-1 (P=0.01) in pre-dialysis CRF patients. Dialysed patients had lower HDL cholesterol (P=0.01) and higher triglyceride (P=0.05) than controls, but LDL-oxidation was similar in all groups. Autoantibodies to oxLDL were raised in angina (P<0.005) and pre-dialysis (P=0.006), but were absent in most dialysed patients. Concentrations of IL-6, TNF-alpha, CRP and fibrinogen were elevated in CRF compared with control and angina patients (P<0.005). In the whole population, IL-6 and TNF-alpha correlated negatively with EDV, HDL cholesterol, and positively with triglyceride, blood pressure, vWf, iCAM-1, vCAM-1 and E-selectin (r=-0.43 to +0.70, all P<0.05). CONCLUSIONS: Endothelial dysfunction is unrelated to LDL oxidation, suggesting that LDL oxidation might not be a major cause of VED in CRF. In contrast VED was more severe in CRF than in angina patients and is associated with increased acute-phase proteins and plasma cytokines, demonstrating a chronic inflammatory state. These observations may explain the VED and increased IHD risk of patients with CRF. 相似文献
3.
Cellular injury or organ dysfunction from oxidative stress occurs when reactive oxygen species (ROS) accumulate in excess of the host defense mechanisms. The deleterious effect of ROS occurs from 2 principal actions. First, ROS can inactivate mitochondrial enzymes, damage DNA, or lead to apoptosis or cellular hypertrophy. Second, nitric oxide (NO), which is a principal endothelial-derived relaxing factor, reacts with superoxide anion (O2-) to yield peroxynitrite (ONOO-), which is a powerful oxidant and nitrosating agent. The inactivation of NO by O2- creates NO deficiency. Oxidative stress can promote the production of vasoconstrictor molecules and primary salt retention by the kidney. Several hypertensive animal models showed increased activity of nicotine adenine dinucleotide phosphate (NADPH) oxidase, which is the chief source of O2- in the vessel wall and kidneys. NO regulates renal blood flow, tubuloglomerular feedback (TGF), and pressure natriuresis. Animal models of NO deficiency develop hypertension, proteinuria, and glomerulosclerosis. Evidence is presented that chronic renal failure (CRF) is a state of NO deficiency secondary to decreased kidney NO production and/or increased bioinactivation of NO by O2-. Patients with CRF show decreased endothelium-dependent vasodilatation to acetylcholine, have increased markers of oxidative stress, and diminished antioxidant activity. Therapy for oxidative stress has focused on antioxidants and agents that modify the renin-angiotensin system. The effects of such treatments are more compelling in animal models than in human studies. 相似文献
4.
Rutkowski P Słominska EM Szołkiewicz M Aleksandrowicz E Smolenski RT Wołyniec W Renke M Wisterowicz K Swierczynski J Rutkowski B 《Scandinavian journal of urology and nephrology》2007,41(3):243-248
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. 相似文献
5.
Ece A Atamer Y Gürkan F Davutoğlu M Bilici M Tutanç M Güneş A 《Pediatric nephrology (Berlin, Germany)》2006,21(2):239-245
Increased oxidative stress is believed to contribute to an increased risk of cardiovascular disease in uraemia. In children with chronic renal failure (CRF), an anti-oxidant enzyme, paraoxonase (PON), that inhibits oxidation of LDL-cholesterol, has not been previously investigated. In this study we aimed to investigate PON activity, total anti-oxidant response (TAR), total peroxide (TPX), oxidative stress index (OSI) and some pro-oxidant cytokines in 29 children with CRF [mean age 10.2±3.5 years; 19 pre-dialysis, ten on continuous ambulatory peritoneal dialysis (CAPD)] and in 25 control subjects. Children with CRF had lower PON and TAR and higher TPX and OSI values than did controls (P<0.05). Except for lower TAR and serum albumin levels of the CAPD subgroup (P<0.05), other parameters were similar in non-dialysis and CAPD patients (P>0.05). Patients had significant positive correlation between TAR and serum albumin (P<0.05). Serum urea had significant positive correlation with TPX and OSI (P<0.05). Increased oxidative stress and decreased anti-oxidants measured by serum PON activity and TAR were found in children with CRF. We can hypothesize, on the basis of statistical correlations, that low levels of serum albumin and high levels of uraemic metabolites might be responsible for increased oxidative stress in children with CRF. Further studies with larger sample sizes are needed to verify these results. 相似文献
6.
Obesity is a risk factor for development of kidney disease. Advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) play important roles in the pathogenesis of renal disorders that are not associated with diabetes. Harcourt et al. provide evidence to support the mechanism responsible for AGE-RAGE interaction and the downstream oxidative stress and inflammation in obesity-related dysfunction. These findings might provide a new strategy for kidney disease in obesity. 相似文献
7.
Vascular erectile dysfunction in chronic renal failure 总被引:1,自引:0,他引:1
The prevalence of erectile dysfunction (ED) has increased dramatically worldwide in parallel with the aging of the population. In 1995, ED was estimated to be present in more than 150 million men. Considering population aging in Western countries, estimates predict that more than 300 million men will be affected by ED by the year 2025. ED is a common and often distressing side effect of renal failure. It is present in 30% of patients with chronic renal failure and in 50% of patients undergoing dialysis treatment. Uremic men of different ages report a high variety of sexual problems including sexual hormonal pattern alterations, reduced or loss of libido, infertility, and impotence, thereby influencing their well-being. The pathogenetic mechanisms include physiologic, psychologic, and organic causes. Since the release of sildenafil citrate, the relationship between ED and the presence of cardiovascular disease (CVD) has been evaluated in several studies. Many of the risk factors for ED are the same as those for cardiac disease. CVD and ED are closely interrelated disease processes. Indeed, ED can be considered a symptom of vascular endothelial damage. Therefore, it can be expected that impotence will appear along with CVD, and the presence of ED suggests the existence of CVD. An accurate evaluation of the sexual histories of all men who present to internists, cardiologists, and also nephrologists for early detection of ED may allow for early diagnosis and management of CVD. 相似文献
8.
Endothelium-dependent vasodilation and oxidative stress in chronic renal failure: impact on cardiovascular disease 总被引:6,自引:0,他引:6
Despite significant progress in renal replacement therapy, the mortality from cardiovascular disease (CVD) in patients with chronic renal failure (CRF) is many times higher than in the general population. The traditional risk factors are frequently present in CRF patients. However, based upon conventional risk factor analysis, these factors do not fully explain the extraordinary increase in morbidity and mortality in CVD among patients with CRF. Accumulating evidence suggests that CRF is associated with impaired endothelial cell function. In recent years, the role of endothelial dysfunction (ED) and excessive oxidative stress (OS) in the development of CVD has been highlighted. ED is an early feature of vascular disease in different diseases such diabetes, hypertension, hypercholesterolemia, and coronary heart disease. The precise mechanism which induces ED is not clear. Several factors however, including OS-related accumulation of uremic toxins, hypertension and shear stress, dyslipidemia with cytotoxic lipoprotein species such as small, dense low-density lipoprotein (LDL) particles, competitive inhibition of endothelial nitric oxide (NO) by increased production by asymmetrical dimethylarginine (ADMA) are pathogenic. In addition, it is known that excessive OS causes ED. An overproduction of reactive oxygen species (ROS) may injure the endothelial cell membrane, inactivate NO, and cause oxidation of an essential cofactor of nitric oxide synthase (NOS). Recent studies have demonstrated that an impaired endothelium-dependent vasodilation and OS are closely related to each other in patients with CRF. 相似文献
9.
Oxidative stress in chronic renal failure 总被引:1,自引:0,他引:1
Martín-Mateo MC Sánchez-Portugal M Iglesias S de Paula A Bustamante J 《Renal failure》1999,21(2):155-167
This study focuses on the oxidative stress in patients with severe chronic renal failure who are not undergoing dialysis treatment. The erythocyte levels, creatinine clearing and plasma- and cell activities of the following enzymes were determined: glutathione peroxidase (Gpx), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione transferase (GT). The concentrations of non-enzyme molecules such as total glutathione in both oxidized and reduced forms, and malonyldialdehyde (MDA) were also measured. The obtained values were compared with those in healthy blood donors of comparable age and social status. The results indicate that chronic renal patients have lower glutathione levels and reduced activities of glutathione peroxidase and of glutathione reductase, while exhibiting elevated levels of malonyldialdehyde and activities of superoxide dismutase, glutathione transferase, and catalase. Finally, creatinine clearing was found to be correlated (p < 0.001) to total (oxidized and reduced) glutathione, Gpx and MDA. These observations may serve to establish a simple protocol for evaluation of renal function. 相似文献
10.
Mohammed Al-Biltagi Osama A. Tolba Maher Ahmed Abd ElHafez Ahmed Abd ElBasset Abo-Elezz Eman Kamel EL Kady Sahar Mohey El-din Hazza 《Pediatric nephrology (Berlin, Germany)》2016,31(8):1329-1339
Objective
The objective of this study was to evaluate cardiac function in children with end-stage renal disease (ESRD) on regular hemodialysis using speckle tracking echocardiography (STE) and correlate results with plasma glutathione level as a marker of oxidative stress.Methods
The study involved 30 children with ESRD and 30 healthy controls. The plasma glutathione and C-reactive protein (CRP) levels were measured, and cardiac function was evaluated using conventional echocardiography and STE.Results
Plasma glutathione levels were significantly lower and CRP significantly higher in patients than in controls. Children with ESRD had significant systolic and diastolic cardiac dysfunctions detected by STE compared with controls. Conventional echocardiography failed to detect these dysfunctions. There was significant increase in left-ventricular relative wall thickness (LV-RWT) in patients, especially those with hypertension, compared with the control group. There was also significant impairment of LV and right-ventricular (RV) global longitudinal strain (GLS) and torsion; however, LV-GLS was significantly better in hypertensive than in normotensive patients. The degree of impairment in GLS and cardiac torsion negatively correlated with plasma glutathione levels.Conclusion
Significant oxidative stress was present in children with ESRD and was correlated with the degree of cardiac dysfunction detected early using the new cardiac imaging modality, STE.11.
BACKGROUND: Chronic kidney disease (CKD) is associated with increased morbidity and mortality in cardiovascular disease (CVD). Apart from traditional risk factors, chronic inflammation, oxidative stress, malnutrition and endothelial dysfunction are important in CVD development in renal patients. Our aim was to investigate the relationship between high sensitivity C-reactive protein (CRP), endothelium dependent vasodilation (EDV) and oxidative stress markers in patients with CKD K/DOQI stage 3-5. METHODS: Measurements of CRP, conjugated dienes (CD), lipid hydroperoxide (LOOH), oxidized low density lipoprotein,glutathione and albumin were performed in 44 consecutive patients with CKD stage 3-5. EDV was measured by methacholine infusion in the brachial artery and venous occlusion plethysmography. RESULTS: Patients with high CRP had significantly lower glomerular filtration rates and albumin, but increased LOOH and CD. In multiple regression analysis, only LOOH and CD remained significant. Patients with poor EDV had increased urea and lower glutathione (GSH). In multiple regression analysis, GSH and urea were independently related to EDV. No correlation was found between CRP and endothelial function. CONCLUSION: CRP was related to lipid peroxidation, while endothelial function was related to intracellular oxidative stress in patients with CKD. CRP and EDV were unrelated to each other. Therefore, CRP and endothelial function could provide complementary prognostic information regarding future cardiovascular disorders in renal patients. 相似文献
12.
目的 探讨奥美沙坦酯对慢性心力衰竭小鼠肾脏氧化应激的作用。 方法 健康C57小鼠分为假手术组(SHAM组)、慢性心力衰竭组(CHF组)和奥美沙坦酯治疗组(OLM组)。以冠状动脉左前降支结扎法建立慢性心力衰竭小鼠模型,其中奥美沙坦酯治疗组以10 mg/kg剂量每日胃饲,12周时观察各组小鼠心率、血压、心功能状况、Scr、BUN、血浆和肾脏血管紧张素(Ang)Ⅱ水平。实时PCR法检测肾脏gp91phox、p22phox和NOX4的表达。AZAN染色和二氢乙啶(DHE)染色观察肾组织病理变化。 结果 与SHAM组比较,CHF组和OLM组左室舒张末期内径(LVDd)和左室收缩末期内径(LVDs)显著增加(P < 0.05);短轴缩短率(FS)和射血分数(EF)显著降低(P < 0.05);CHF组收缩压、Scr和BUN显著增高,而OLM组以上指标较CHF组均显著降低(P < 0.05)。与SHAM组比较,CHF组血浆和肾脏AngⅡ水平增高,gp91phox、p22phox和NOX4表达增高(P < 0.05);OLM组肾脏AngⅡ水平、gp91phox、p22phox和NOX4表达较CHF组均显著降低(P < 0.05)。与SHAM组比较,CHF组肾脏AZAN染色和DHE染色阳性增强(P < 0.05),而OLM组较CHF组显著降低(P < 0.05)。 结论 慢性心力衰竭可使肾内NADPH氧化酶激活并导致肾小球间质纤维化,奥美沙坦酯通过抑制AngⅡ引起的氧化应激反应起到肾脏保护作用。 相似文献
13.
Erythrocyte susceptibility to oxidative stress in chronic renal failure patients under different substitutive treatments 总被引:5,自引:0,他引:5
Lucchi L Bergamini S Iannone A Perrone S Stipo L Olmeda F Caruso F Tomasi A Albertazzi A 《Artificial organs》2005,29(1):67-72
An increased oxidative stress is now considered one of the major risk factors in chronic renal failure (CRF) patients that may be exacerbated by dialysis. It has been postulated that this increased oxidative stress might cause an augmented red blood cell (RBC) membrane lipid peroxidation with the consequent alteration in membrane deformability. The aim of this study was to evaluate RBC susceptibility to an in vitro induced oxidative stress and RBC antioxidant potential in different groups of CRF patients undergoing different substitutive treatment modalities. Fifteen end-stage CRF patients were evaluated in conservative treatment, 23 hemodialysis (HD) patients, 15 continuous ambulatory peritoneal dialysis (CAPD) patients, 15 kidney transplanted patients, and 16 controls. Their RBCs were incubated with the oxidative stress-inducing agent tert-butylhydroperoxide both in the presence and in the absence of the catalase inhibitor sodium azide, and the level of malondialdehyde (MDA) (a product of lipid peroxidation), was measured at 0, 5, 10, 15, and 30 min of incubation. In addition, the RBC content of reduced glutathione (GSH) was measured by HPLC. As opposed to the controls, RBCs from end-stage CRF patients exhibited an increased sensitivity to oxidative stress induced in vitro, both in the absence and presence of a catalase inhibitor, as demonstrated by a significantly higher level of MDA production at all the incubation times (P < 0.05). Different substitutive treatments had different impacts on this phenomenon; CAPD and kidney transplantation were able to normalize this alteration while HD was not. GSH appeared to be related to the increase in RBC susceptibility to oxidative stress; its content being significantly elevated in end-stage CRF and HD patients as compared with CAPD and transplanted patients and controls (P < 0.05). No significant changes were observed in the RBC glutathione content during the HD session. The increase of GSH in RBCs of end-stage CRF and HD patients seems to indicate the existence of an adaptive mechanism under increased oxidative stress occurring in vivo. Unlike HD, the beneficial effect of CAPD on the anemia of dialysis patients might partly be due to a condition of lower oxidative stress that might in addition counterbalance the cardiovascular negative effects of dislipidemia of CAPD patients. 相似文献
14.
15.
Carluccio F Siems W Stefanelli G Sommerburg O Grune T Riedel E Hampl H 《Clinical nephrology》2002,58(Z1):S26-S30
Homocysteine serum levels were measured in patients with end-stage renal disease in relation to severity of renal anemia and oxidative stress parameters such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA). The predialytic homocysteine serum levels of the patients are five times as high as in healthy controls. It was found that homocysteine does not correlate to hemoglobin concentration and to oxidative stress, but rather to parameters of nutrition status such as albumine concentration and protein catabolic rate. The homocysteine accumulation represents a cardiovascular risk factor which is statistically independent of oxidative stress, but dependent on nutrition or energy status in patients with chronic renal failure. 相似文献
16.
Oxidative stress in chronic renal failure. 总被引:6,自引:1,他引:5
J Galle 《Nephrology, dialysis, transplantation》2001,16(11):2135-2137
17.
The effect of serum albumin level on iron-induced oxidative stress in chronic renal failure patients 总被引:1,自引:0,他引:1
BACKGROUND: Intravenous iron (IVIR) administration is widely used to treat anemia in chronic renal failure (CRF) patients and causes oxidative stress. Despite the fact that proteins are extremely susceptible to oxidative stress, there have been no studies investigating the relationship between the severity of iron-induced acute oxidative stress and serum albumin. Therefore, we wanted to investigate the relation between the severity of iron-induced acute oxidative stress and serum albumin level in CRF patients. METHODS: A total of 68 patients (22 on hemodialysis, 24 on continuous ambulatory peritoneal dialysis and 22 predialytic CRF) with absolute iron deficiency were included to the study. Patients with acute inflammatory status, serum ferritin level > or = 100 ng/mL, transferrin saturation > or = 20%, hemoglobin level > or = 12 g/dL or serum C-reactive protein (CRP) level > or = 10 mg/dL were excluded. Serum direct 8-isoprostoglandin F2 alpha (IsoPG-F2 alpha) level was used as an oxidative stress marker. After baseline sampling, 100 mg ferric sucrose was infused within 30 minutes. Blood samples were drawn to assess changes in oxidative stress marker at the end of the IVIR infusion and at 240 minutes. Patients with serum albumin level <4 g/dL were defined as hypoalbuminemic and > or = 4 g/dL as normoalbuminemic. RESULTS: There were 34 hypoalbuminemic and 34 normoalbuminemic patients. Serum IsoPG-F2 alpha level increased in all patients after the administration of IVIR. The severity of iron-induced acute oxidative stress was more prominent in patients with a low serum albumin level. Serum albumin level, presence of diabetes mellitus (DM) and hemoglobin level were found as significant predictors of time-dependent changes in serum IsoPG-F2 alpha level. When the analyses were repeated in nondiabetic patients, serum albumin level was similarly found to be a significant predictor of time-dependent changes in serum IsoPG-F2 alpha level. CONCLUSION: This study demonstrated a negative interaction between iron-induced acute oxidative stress and serum albumin level in CRF patients. Because CRF patients with low serum albumin level are at greater risk for iron-induced acute oxidative stress, new strategies are necessary in this population. 相似文献
18.
Patients with renal hypouricemia with exercise-induced acute renal failure and chronic renal dysfunction 总被引:4,自引:0,他引:4
Kikuchi Y Koga H Yasutomo Y Kawabata Y Shimizu E Naruse M Kiyama S Nonoguchi H Tomita K Sasatomi Y Takebayashi S 《Clinical nephrology》2000,53(6):467-472
We here report the case of a 38-year-old male with back pain and vomiting occurring after exercise. Serum creatinine level was elevated, and he was admitted to our hospital with diagnosis of acute renal failure (ARF). He had experienced similar attacks at least 4 times, including the present episode, from the age of 22 years. After admission, the patient was managed only by resting, and remission was nearly attained in about 1 month. The renal biopsy specimen performed on day 15 showed findings of acute tubular necrosis, thickening of the tubular basement membrane, and interstitial fibrosis. After remission, the serum uric acid level was 0.7-0.8 mg/dl, fractional excretion of uric acid was 0.63, and the possibility of other diseases facilitating the excretion of uric acid was denied. Therefore, ARF associated with idiopathic renal hypouricemia was diagnosed. Since only mild responses were observed in a pyradinamide loading test and a benzbromarone loading test, the case was considered to be a presecretary reabsorption disorder type. Renal function tests showed the almost complete recovery of the glomerular filtration rate (GFR: 114 ml/min/1.73 m2), but the urine concentrating ability was markedly decreased (specific gravity 1.019 and osmolarity 516 mOsm/kgxH2O in Fishberg test). Past data from this patient indicated that this renal dysfunction had been persisting for ten years. We examined 9 patients with renal hypouricemia and focused on the differences between the two groups (with or without complications). Four patients had a history of exercise-induced ARF or calculus. The urine concentrating ability was significantly lower in these patients (group A) than in the other patients without complications (group B). The glomerular filtration rate in group A was within the normal range, but was lower than in group B. These results suggested the possibility that patients with renal hypouricemia with complications may have chronic renal dysfunction in the future. 相似文献
19.
Salvage of cyclosporine A-induced oxidative stress and renal dysfunction by carvedilol 总被引:3,自引:0,他引:3
BACKGROUND: Cyclosporine A (CsA) is the first-line immunosuppressant employed for the management of solid organ transplantation and autoimmune diseases. Nephrotoxicity is the major limitation of CsA use. Recent evidence suggests that reactive oxygen species (ROS) play an important role in mediating CsA nephrotoxicity. The present study was designed to investigate effects of carvedilol, a third-generation beta-blocker with potent free radical-scavenging activity on CsA-induced oxidative stress and resultant renal dysfunction in a rat model of chronic CsA nephrotoxicity. METHODS: Carvedilol (2.0 and 4.0 mg/kg i.p.) and propranolol (10 mg/kg i.p.) were administered to separate group of animals 24 h before and concurrently with CsA (20 mg/kg s.c.) for 21 days. Renal function was assessed by estimating plasma creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Tissue lipid peroxidation was measured as thiobarbituric acid-reacting substances (TBARS). Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin, PAS and Masson's trichrome stained sections of the kidneys. RESULTS: CsA (20 mg/kg s.c) administration for 21 days produced elevated levels of TBARS and deteriorated renal function as assessed by increased plasma creatinine, BUN and decreased creatinine and urea clearance as compared to vehicle-treated rats. The kidneys of CsA-treated rats showed severe striped interstitial fibrosis, arteriolopathy, glomerular basement thickening, tubular vacuolization and hyaline casts. Propranolol neither decreased TBARS nor improved the renal dysfunction and morphological changes induced by CsA. Both doses of carvedilol markedly reduced elevated levels of TBARS, whereas the higher dose of carvedilol significantly attenuated renal dysfunction and morphological changes in CsA-treated rats. CONCLUSIONS: These data clearly indicate the renoprotective potential of carvedilol in CsA-induced nephrotoxicity and suggest a significant contribution of its antilipoperoxidative property in this beneficial effect. 相似文献
20.
Endothelial dysfunction and damage are systemic processes that are recognised to play a central role in the pathogenesis of hypertension and atherosclerotic cardiovascular disease. Renal failure is associated with impaired endothelium dependent vasodilatation that is partly a consequence of increased circulating levels of asymmetric dimethyl arginine. Endothelial dysfunction persists, although it is improved, after renal transplantation. Statins appear to improve endothelial dysfunction, as does withdrawal of calcineurin inhibitors, although there is no evidence that these strategies improve patient or graft survival. The situation in transplant recipients is complicated by the fact that endothelial dysfunction (within the graft vasculature) may be a separate process contributing to chronic allograft nephropathy and to circulating levels of endothelial cells and their components, thus limiting the utility of circulating markers of endothelial damage in this population. 相似文献