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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two groups of patients with insulin-dependent diabetes mellitus of > 10 years duration and either persistent normoalbuminuria (group 1, n = 49; albumin excretion < 30 mg/day) or microalbuminuria (group 2, n = 33; albumin excretion 30-300 mg/day) were investigated for evidence of free oxygen radical activity (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl-glucosaminidase and leucine aminopeptidase) were also measured. Healthy controls (n = 38) were matched for age and sex. Groups 1 and 2 were similar in terms of age, sex, duration of diabetes and recent glycaemic control. Serum cholesterol and creatinine were similar in all three groups. Free-radical activity and oxidant injury were significantly higher in groups 1 and 2 than in controls (p < 0.001). Glomerular proteinuria, tubular proteinuria and enzymuria were significantly higher in group 2 than in group 1 and controls (p < 0.01). Group 1 had significantly higher transferrinuria, tubular enzymuria and tubular proteinuria than controls. However, groups 1 and 2 were similar in degree of free oxygen radical generation and oxidant injury. In diabetic nephropathy, oxidant injury and renal tubular damage accompany and may even precede microalbuminuria. The presence of these abnormalities in the absence of glomerular proteinuria favours the hypothesis that alterations first occur in the peritubular microcirculation, which by causing oxidant injury and tubular damage, may initiate diabetic nephropathy.
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PMID:Evidence of oxidant injury and tubular damage in early diabetic nephropathy. 798 55

1. Diabetic nephropathy is a serious microvascular complication in patients with insulin-dependent diabetes mellitus, resulting in end-stage renal disease in 30-45% of such patients. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and free-radical activity may be important factors. 2. Forty normotensive patients with insulin-dependent diabetes mellitus of between 10 and 20 years duration with persistent normoalbuminuria (albumin excretion < 30 mg/day) and normal renal function were investigated for markers of endothelial dysfunction (plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity), free oxygen radical generation (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl glucosaminidase and leucine aminopeptidase) were also measured. 3. Patients were divided into two groups. Group 1 comprised 21 patients with elevated markers of endothelial dysfunction, and group 2 comprised 19 patients with normal levels of plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity. Thirty-eight healthy subjects matched for age and sex acted as controls. 4. Groups 1 and 2 were similar in age, sex, body weight, duration of diabetes mellitus and recent glycaemic control. Serum cholesterol, serum creatinine and glomerular proteinuria were similar in the three groups. Group 1 patients had significantly increased oxidant injury, tubular enzymuria and proteinuria compared with group 2 patients and control subjects (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between markers of endothelial dysfunction, oxidant injury and tubular damage in patients with insulin-dependent diabetes mellitus. 828 43

The aim of this study was to analyse the effect of angiotensin convertase inhibitor, enalapril (ENA), and angiotensin AT-1 receptor antagonist, losartan potassium (LP), on lipid peroxidation and activities of Cu,Zn-superoxide dismutase, catalase and glutathione peroxidase in kidneys of streptozotocin (STZ)-induced diabetic rats after 6 and 12 weeks of treatment. STZ-induced body weight changes and blood glucose concentration were not affected by either ENA or LP but both drugs significantly decreased cholesterol and triglyceride concentrations elevated in diabetic rats, inhibited kidney weight gain, and decreased albuminuria. Kidneys of STZ-diabetic rats had increased malondialdehyde content and decreased activities of antioxidant enzymes (Cu,Zn-superoxide dismutase, catalase and glutathione peroxidase). Both ENA and LP decreased lipid peroxidation and augmented the activities of antioxidant enzymes studied in the kidneys of diabetic rats. These results confirm the role of oxidative stress in the development of diabetic nephropathy already at early stages of the development of diabetes and point to the possible antioxidative mechanism of the nephroprotective action of ENA and LP.
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PMID:Effect of angiotensin convertase inhibitors and AT1 angiotensin receptor antagonists on the development of oxidative stress in the kidney of diabetic rats. 1050 93

Oxidative stress is implicated in the pathogenesis of diabetic nephropathy. The attempts to identify early markers of diabetes-induced renal oxidative injury resulted in contradictory findings. We characterized early oxidative stress in renal cortex of diabetic rats, and evaluated whether it can be prevented by the potent antioxidant, DL-alpha-lipoic acid. The experiments were performed on control rats and streptozotocin-diabetic rats treated with/without DL-alpha-lipoic acid (100 mg/kg i.p., for 3 weeks from induction of diabetes). Malondialdehyde plus 4-hydroxyalkenal concentration was increased in diabetic rats vs. controls (p <.01) and this increase was partially prevented by DL-alpha-lipoic acid. F(2) isoprostane concentrations (measured by GCMS) expressed per either mg protein or arachidonic acid content were not different in control and diabetic rats but were decreased several-fold with DL-alpha-lipoic acid treatment. Both GSH and ascorbate (AA) levels were decreased and GSSG/GSH and dehydroascorbate/AA ratios increased in diabetic rats vs. controls (p <.01 for all comparisons), and these changes were completely or partially (AA) prevented by DL-alpha-lipoic acid. Superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione transferase, and NADH oxidase, but not catalase, were upregulated in diabetic rats vs. controls, and these activities, except glutathione peroxidase, were decreased by DL-alpha-lipoic acid. In conclusion, enhanced oxidative stress is present in rat renal cortex in early diabetes, and is prevented by DL-alpha-lipoic acid.
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PMID:Early oxidative stress in the diabetic kidney: effect of DL-alpha-lipoic acid. 1252

Numerous reports have demonstrated that oxidative stress induced by diabetes plays an important role in the development and progression of diabetic vascular complications including nephropathy. Indeed, there is emerging evidence that the formation of reactive oxygen species (ROS) is a direct consequence of hyperglycemia. Biomarkers for oxidative damage to DNA, lipids, and proteins are also supporting the concept of increased oxidative stress in diabetes and diabetic nephropathy. However, there is an unanswered question: When does oxidative stress as a pathogenetic event occur in the process of diabetic nephropathy? To answer this question, glomerular ROS was imaged with the use of 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The image of DCF fluorescence was strong in glomeruli from diabetic rats as compared with that of glomeruli from nondiabetic control rats. mRNA expression of antioxidant enzymes such as catalase, glutathione peroxidase, Cu/Zn superoxide dismutase, and heme oxygenase-1 (HO-1) was also determined because oxidative stress definitely refers to the situation of an imbalance between the production of ROS and antioxidant defense. The mRNA expression of catalase, glutathione peroxidase, and Cu/Zn superoxide dismutase 2 wk after the induction of diabetes was not significantly different from that in control rats. Alternatively, mRNA and protein expression of HO-1 was strongly induced by 16-fold in diabetic glomeruli after the induction of diabetes. Antioxidant treatment with either vitamin E or probucol almost completely normalized HO-1 overexpression in diabetic glomeruli, supporting the existence of oxidative stress in the glomeruli of early diabetes. Furthermore, It has reported that antioxidant treatment with vitamin E, probucol, alpha-lipoic acid, or taurine normalized diabetes-induced not only renal dysfunction such as albuminuria and glomerular hypertension but also glomerular pathologies. In summary, oxidative stress by diabetes could play a crucial role in the development and progression of diabetic nephropathy, and antioxidant treatment could be a potential therapeutic procedure for diabetic nephropathy.
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PMID:Effects of antioxidants in diabetes-induced oxidative stress in the glomeruli of diabetic rats. 1287 41

The aim of this study was to analyze the effect of vitamins C and E on malondialdehyde (MDA) content and activities of key antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as glomerular basement membrane (GBM) thickness in streptozotocin-induced diabetic kidney in rats. Wistar male rats were divided into following groups (12 rats each): the control, diabetic rats, diabetic rats whose drinking water was supplemented with vitamin C in a dose of 1.0 g/l or diet was supplemented with 200 mg of vitamin E/100 g fodder. Body weight, blood glucose and HbA1C levels and 24-hour urinary albumin excretion (UAE) were studied every week (0-12 weeks). After 6 and 12 weeks, MDA content and activities of SOD, CAT and GSH-Px were measured in the kidney homogenate supernatants. Electron micrographs of glomeruli were scanned and morphometric investigations were performed by means of computer image analysis system to compare GBM thickness. The blood glucose and HbA1C concentrations and UAE in diabetic rats were significantly higher than in the control group. An increase in the MDA level and decrease in the SOD, CAT and GSH-Px activities in the kidney of diabetic rats were observed after 6 and 12 weeks of experiment. Administration of vitamins C and E did not affect body weight, blood glucose and HbA1C levels. Both vitamin C and vitamin E decreased lipid peroxidation and augmented the activities of antioxidant enzymes studied in the kidneys of diabetic rats as well as reduced UAE, decreased kidney weight and GBM thickness. The results indicate the potential utility of antioxidant vitamins in the protection against the development of diabetic nephropathy.
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PMID:Effect of vitamin E and vitamin C supplementation on antioxidative state and renal glomerular basement membrane thickness in diabetic kidney. 1469 67

To investigate the status and role of glutathione peroxidase (GPX) in diabetic nephropathy, we measured GPX in the plasma and urine of 14 patients with diabetic glomerulosclerosis (DGS) and measured glomerular GPX immunostaining in these patients and in rats with streptozotocin-induced diabetes of varying duration. Plasma GPX levels were significantly lower in DGS patients than in diabetic patients without nephropathy (P < .05) or normal controls (P < .01). Urinary GPX concentrations were also significantly lower in DGS patients than in diabetic patients without nephropathy or normal controls (both P < .05). Immunostaining of glomerular GPX was significantly less in DGS patients than in normal controls (P < .05) and was negatively correlated with the glomerular sclerosis score and the index of mesangial expansion. Serial examination of glomerular GPX in diabetic rats showed that immunostaining scores for glomerular GPX in rats were significantly lower than those in normal control rats after 1 and 3 months' duration of diabetes, and staining scores were also significantly lower in rats killed after 3 months of diabetes than in those killed after 1 week. In conclusion, our study demonstrates that GPX concentrations in plasma, urine, and glomeruli are decreased in individuals with DGS and that the immunostaining of glomerular GPX decreases progressively.
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PMID:Alterations of glomerular and extracellular levels of glutathione peroxidase in patients and experimental rats with diabetic nephropathy. 1596 36

Oxidative stress has an important role in genesis of diabetic complications, especially diabetic nephropathy. The aim of the study was to assess correlations between increase of oxidative stress (OS) and the development of microalbuminuria (MA) in type 1 diabetic patients. We determined the oxidative status by measuring the level of superoxide dismutase (SOD-Minanui method), catalase (CAT-Aebi method), glutathione peroxidase (GPx-Fukuzawa method) and glutathione (GSH-Ellman method) in 87 type 1 diabetic patients (44 with normal urinary protein excretion-group A and 43 with MA-group B) and 38 nondiabetic matched controls, before and 24 hours after a test effort. The results of the study point out that a decreased in activity of SOD or in levels of GSH is associated with an increased MA in type 1 diabetic patients.
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PMID:[Correlation between increase of oxidative stress and microalbuminuria in type-1 diabetic patients]. 1600 16

We have studied the effects of red wine on brain oxidative stress and nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Wistar rats with a single intraperitonally injection of STZ (50 mg/kg). Two weeks before and four weeks after injection, red wine was given orally in both normal and diabetic rats. Blood samples were taken from the neck vascular trunk in order to determine the glucose, triglycerides, total cholesterol, HDL-cholesterol (HDL-c), atherogenic index (AI), total protein, blood urea nitrogen (BUN), creatinine, insulin, lipid peroxidation products, reduced glutathione (GSH) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. As well, we estimated the lipid peroxidtion, GSH and SOD, GSH-Px and catalase activities in brain and renal homogenates, and the excretion of albumin, proteins and glucose in urine over 24 h period. The administration of STZ caused significant increases in levels of glycosuria, proteinuria, albuminuria, glycemia, total cholesterol and AI, as well as in lipid peroxidation products in the brain, plasma and kidney, whereas it decreased the GSH content and SOD, GSH-Px and catalase activities. Treatment with red wine significantly prevented the changes induced by STZ. These data suggested that red wine has a protective effect against brain oxidative stress, diabetic nephropathy and diabetes induced by STZ, as well as it protects against hypercholesterolemia and atherogenic risk.
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PMID:Red wine prevents brain oxidative stress and nephropathy in streptozotocin-induced diabetic rats. 1620 32

1. Increased oxidative stress has an important role in the pathogenesis of diabetic nephropathy. The aim of the present study was to evaluate diabetic nephropathy by determining markers of oxidative stress and the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), albumin and to investigate the possible protective effects of in vivo melatonin on renal tubular oxidative damage in diabetic rats. 2. Twenty-six rats were randomly divided into three groups: (i) group I, control, non-diabetic rats (n = 9); (ii) group II, untreated diabetic rats (n = 8); and (iii) group III, melatonin-treated diabetic rats (n = 9). In groups II and III, diabetes developed 3 days after administration of a single dose of streptozotocin (35 mg/kg, i.p.). Thereafter, whereas the rats in group II received no treatment, rats in group III began to receive 10 mg/kg per day, i.p., melatonin for 8 weeks. Malondialdehyde (MDA), an index of lipid peroxidation, NAG and microalbumin in the urine, markers of renal tubular damage, were the parameters used for oxidative stress-induced renal injury. Superoxide dismutase (SOD), xanthine oxidase (XO) and glutathione peroxidase (GSH-Px) activities were determined to evaluate changes in the anti-oxidant status of kidney tissue. 3. In untreated diabetic rats, urinary NAG, albumin and renal MDA levels were markedly increased compared with control rats (P < 0.0001). However, these parameters were reduced in diabetic rats by melatonin treatment (P < 0.0001). Urinary excretion of NAG was positively correlated with the microalbuminuria and renal MDA levels (r = 0.8; P < 0.0001). The SOD and XO activities in the untreated diabetic group were found to be significantly higher than those of the control group (P < 0.0001). Superoxide dismutase and XO activities decreased in melatonin-treated rats compared with untreated diabetic rats (P < 0.002 and P < 0.023, respectively). However, the decrease did reach levels seen in control rats. There were no significant differences in GSH-Px activity between the three groups. 4. Therefore, on the basis of these data, we suggest that urinary NAG, albumin excretion, XO activity and MDA levels are more valuable parameters showing the degree of renal tubular injury than classical markers of oxidative stress, including SOD and GSH-Px, in diabetic rat kidneys. Melatonin has an ameliorating effect on oxidative stress-induced renal tubular damage via its anti-oxidant properties. Thus, it may be suggested that urinary NAG excretion and microalbuminuria may be important markers showing the degree of renal changes and the success of long-term treatment of renal impairment with melatonin.
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PMID:Melatonin reduces urinary excretion of N-acetyl-beta-D-glucosaminidase, albumin and renal oxidative markers in diabetic rats. 1644 6


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