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

Recent evidences indicate a pivotal role of reactive oxygen species in etiology of diabetic nephropathy, an important microvascular complication of diabetes mellitus. Moreover, oxidative stress leads to an increased production of lipoxygenase derivatives which also play a role in diabetic nephropathy. The present study was thus designed to examine the effect of an antioxidant and a lipoxygenase inhibitor, nordihydroguairetic acid (NDGA), on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg) in rats. After the 4th week of STZ injection, NDGA (5 and 10 mg/kg) was given subcutaneously (s.c.) for another 4 weeks to both control and diabetic rats. At the end of the 8th week, diabetic rats exhibited renal dysfunction as evidenced by reduced creatinine and urea clearance along with enhanced albumin excretion rate as compared with control rats. Biochemical analysis of kidneys revealed a marked increase in oxidative stress demonstrated by increased lipid peroxidation and decreased activities of key antioxidant enzymes, glutathione (GSH), superoxide dismutase (SOD) and catalase in diabetic rats. Chronic treatment with NDGA in diabetic rats significantly prevented both renal dysfunction and oxidative stress as compared with vehicle-treated diabetic rats. The kidneys of diabetic rats showed morphological changes such as hyaline casts, glomerular thickening and moderate interstitial fibrosis and arteriolopathy, whereas NDGA administration in diabetic rats markedly prevented renal morphological alterations. These results emphasize the role of oxidative stress in the pathophysiology of diabetic nephropathy and point towards the potential of NDGA as a complementary therapy for the prevention/treatment of diabetic nephropathy.
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PMID:Nordihydroguairetic acid, a lignin, prevents oxidative stress and the development of diabetic nephropathy in rats. 1529 54

Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. To evaluate the effects on IAP of vitamin E administration in adolescents with type 1 diabetes and early signs of microangiopathy, 12 adolescents (aged 11-21 y; diabetes duration 10-18) were studied. Eight had retinopathy [background (four), preproliferative (three), or proliferative (one)], four had persistent microalbuminuria, and seven had both. Skin fibroblasts were obtained by biopsies and cultured in Dulbecco's modified Eagle's medium. CuZn superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione-peroxidase (GPX) activity and mRNA expression were measured before and after 3 mo of synthetic vitamin E supplementation (600 mg twice daily); on both occasions, IAP was evaluated at different ex vivo glucose concentrations (5 and 22 mM). Ten adolescents with type 1 diabetes (aged 12-20 y) without angiopathy and eight healthy volunteers (aged 15-22 y) participated as control subjects. Vitamin E serum levels were measured throughout the study. In normal glucose concentrations, CuZnSOD, MnSOD, CAT, and GPX activity and mRNA expression were not different among the groups. In high glucose, CuZnSOD activity and mRNA increased similarly in all groups [angiopathics: 0.96 +/- 0.30 U/mg protein; 9.9 +/- 3.2 mRNA/glyceraldehyde-3-phosphate dehydrogenase). CAT and GPX activity and mRNA did not increase in high glucose only in adolescents with angiopathy (0.35 +/- 0.09; 4.2 +/- 0.1 and 0.52 +/- 0.14; 2.4 +/- 0.9, respectively). MnSOD did not change in any group. Vitamin E supplementation had no effect on any enzymatic activity and mRNA in both normal and hyperglycemic conditions. Adolescents with early signs of diabetic angiopathy have defective IAP and activity, which are not modified by vitamin E.
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PMID:Effects of vitamin E supplementation on intracellular antioxidant enzyme production in adolescents with type 1 diabetes and early microangiopathy. 1534 73

Oxidative stress plays an important role in the pathogenesis of renal diseases such as diabetic nephropathy. The metabolism of excessive intracellular glucose may involve a number of processes. One consequence of excessive intracellular glucose levels is an increased rate of oxidative phosphorylation under hyperglycemic conditions, whereas another consequence is an increase in the metabolism of glucose to sorbitol by aldose reductase. In addition, hyperglycemia may result in the activation of NADPH oxidase, the production of superoxide anion, and hydrogen peroxide (H2O2). In this report, we investigate the mechanisms responsible for the H2O2 production that occurs as the consequence of hyperglycemia and the effect of H2O2 on the activity of the Na+/glucose cotransport system (SGLT) in primary cultures of renal proximal tubule cells (PTCs). When primary PTCs were cultured in the presence of high glucose, one consequence was that the Na+/glucose cotransport system was inhibited, as indicated by uptake studies utilizing alpha-methyl-D-glucoside (alpha-MG), a nonmetabolizable analog of D-glucose. Pretreatment of the cultures with either 1) aminoguanidine or pyridoxamine [inhibitors of the accumulation of advanced glycation end products (AGEs)], 2) rotenone (an inhibitor of the mitochondrial electron transport chain), or 3) apocynin or diphenylene iodonium (DPI; inhibitors of NADPH oxidase) blocked the observed changes that occurred as a consequence of the incubation of the PTCs with high glucose. Included among these changes were the observed increase in H2O2 levels, as well as an increase in lipid peroxide production, and a decrease both in the activity of catalase and in the level of glutathione (GSH), endogenous antioxidants. The high glucose-induced decrease in the level of the Na+/glucose cotransporter was similarly prevented by either aminoguanidine, rotenone, or apocynin. Thus the inhibitory effect of high glucose on both the level of the Na+/glucose cotransport system and the activity of the Na+/glucose cotransport system can be explained, at least in part, as being due to the effects of the H2O2, the consequent formation of AGEs, the increase in mitochondrial metabolism, and in NADPH oxidase activity in the PTCs. Other related changes observed in the PTCs that could be reversed by treatment with either aminoguanidine, pyridoxamine, rotenone, apocynin, or DPI included an increase in transforming growth factor-beta1 secretion and the activation of the NF-kappaB signal transduction pathway.
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PMID:High glucose-induced oxidative stress inhibits Na+/glucose cotransporter activity in renal proximal tubule cells. 1559 43

In many diseases, including progressive renal disorders, tissue injury and pathological intracellular signaling events are dependent on oxidative stress. Glutathione peroxidase-1 (Gpx1) is an antioxidant enzyme that is highly expressed in the kidney and removes peroxides and peroxynitrite that can cause renal damage. Therefore, we examined whether this abundant renal antioxidant enzyme limits renal damage during the development of type 1 diabetic nephropathy. Wild-type (Gpx1+/+) and deficient (Gpx1-/-) mice were made diabetic by intraperitoneal injection of streptozotocin (100 mg/kg) on 2 consecutive days. Diabetic Gpx1+/+ and -/- mice with equivalent blood glucose levels (23 +/- 4 mM) were selected and examined after 4 mo of diabetes. Compared with normal mice, diabetic Gpx1+/+ and -/- mice had a two- to threefold increase in urine albumin excretion at 2 and 4 mo of diabetes. At 4 mo, diabetic Gpx1+/+ and -/- mice had equivalent levels of oxidative renal injury (increased kidney reactive oxygen species, kidney lipid peroxidation, urine isoprostanes, kidney deposition of advanced glycoxidation, and nitrosylation end products) and a similar degree of glomerular damage (hypertrophy, hypercellularity, sclerosis), tubular injury (apoptosis and vimentin expression), and renal fibrosis (myofibroblasts, collagen, TGF-beta excretion). A lack of Gpx1 was not compensated for by increased levels of catalase or other Gpx isoforms in diabetic kidneys. Contrary to expectations, this study showed that the high level of Gpx1 expressed in the kidney is not protective against the development of renal oxidative stress and nephropathy in a model of type 1 diabetes.
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PMID:Kidney expression of glutathione peroxidase-1 is not protective against streptozotocin-induced diabetic nephropathy. 1582 46

Diabetic nephropathy is the main cause of end stage renal damage. Oxidative stress is involved in the etiology of diabetic nephropathy and intracellular calcium is reported to play a considerable role in the development of renal damage in the diabetic kidney. Calcium antagonism can slow the progression of renal impairment in diabetes. The present study was thus designed to examine the effect of a nondihydropyridine calcium channel blocker, diltiazem, on renal function, oxidative stress, and nitric oxide (NO) release in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, the rats were divided in to four groups: control rats, diabetic rats treated with saline, and two groups of diabetic rats treated with diltiazem (5 and 10 mg/kg, i.p, respectively) for 8 weeks starting from 4 weeks after STZ injection. Renal function was assessed by creatinine, blood urea nitrogen, creatinine clearance, and urea clearance. Oxidative stress was measured by renal malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase. We also measured renal nitrite levels. At the end of the 8 weeks, diabetic rats exhibited renal dysfunction as evidenced by reduced creatinine and urea clearance along with enhanced albumin excretion rate as compared with control rats. Biochemical analysis of kidneys revealed a marked increase in oxidative stress demonstrated by increased lipid peroxidation and decreased activities of key antioxidant enzymes, GSH, SOD, and catalase in diabetic rats. Release of NO also significantly higher in diabetic rats than controls. Chronic treatment with diltiazem in diabetic rats significantly attenuated both renal dysfunction and oxidative stress along with increased NO levels as compared with untreated diabetic rats. The kidneys of diabetic rats showed morphological changes such as hyaline casts, glomerular thickening, and moderate interstitial fibrosis and arteriolopathy, whereas diltiazem administration markedly prevented diabetic-induced renal morphological alterations. The present study suggests that oxidative stress/nitrosative stress is increased in the diabetic kidney and calcium channel blockage can prevent these changes. The results also suggest that in STZ-induced diabetic rats, the protective action of diltiazem might be mediated, at least in part, by its effect on tissue oxidant/antioxidant status.
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PMID:Diltiazem attenuates oxidative stress in diabetic rats. 1595 52

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

Several lines of evidence, including familial aggregation, suggest that allelic variation contributes to risk of diabetic nephropathy. To assess the evidence for specific susceptibility genes, we used the transmission/disequilibrium test (TDT) to analyze 115 candidate genes for linkage and association with diabetic nephropathy. A comprehensive survey of this sort has not been undertaken before. Single nucleotide polymorphisms and simple tandem repeat polymorphisms located within 10 kb of the candidate genes were genotyped in a total of 72 type 1 diabetic families of European descent. All families had at least one offspring with diabetes and end-stage renal disease or proteinuria. As a consequence of the large number of statistical tests and modest P values, findings for some genes may be false-positives. Furthermore, the small sample size resulted in limited power, so the effects of some tested genes may not be detectable, even if they contribute to susceptibility. Nevertheless, nominally significant TDT results (P < 0.05) were obtained with polymorphisms in 20 genes, including 12 that have not been studied previously: aquaporin 1; B-cell leukemia/lymphoma 2 (bcl-2) proto-oncogene; catalase; glutathione peroxidase 1; IGF1; laminin alpha 4; laminin, gamma 1; SMAD, mothers against DPP homolog 3; transforming growth factor, beta receptor II; transforming growth factor, beta receptor III; tissue inhibitor of metalloproteinase 3; and upstream transcription factor 1. In addition, our results provide modest support for a number of candidate genes previously studied by others.
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PMID:Assessment of 115 candidate genes for diabetic nephropathy by transmission/disequilibrium test. 1624 59

Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. Various studies have revealed that increased oxidative stress is a major pathophysiological mechanism which is involved in the etiology of diabetic nephropathy. Resveratrol, a polyphenolic phytoalexin present in red wine, is known to possess potent antioxidant properties and thus we aimed to examine its effect on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were divided into four groups: the control rats, diabetic rats and diabetic rats treated with resveratrol (5 and 10 mg/kg, orally) respectively from week 4 up till week 6. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The levels of the renal oxidative stress markers malonaldehyde and glutathione and the antioxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. STZ-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in body weight compared with age-matched control rats. After 6 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key antioxidant enzymes. Treatment with resveratrol significantly attenuated renal dysfunction and oxidative stress in diabetic rats. The present study reinforces the important role of oxidative stress in diabetic kidney and points towards the possible antioxidative mechanism being responsible for the renoprotective action of resveratrol.
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PMID:Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats. 1628 9

It has been known that oxidative stress plays an important role in the development of diabetic nephropathy (DN). The antioxidative effects of Astragalus saponin I (AS I) were studied in vitro and in vivo. In the presence of high glucose and H2O2, the total antioxidative capability, catalase, reduced glutathione, and superoxide dismutase level of rat mesangial cells were significantly decreased, and transforming growth factor beta1 (TGF-beta1) mRNA level, collagen IV, and laminin level were significantly increased. When compared with those in the high glucose group, these 4 indexes of cells incubated in 2.0 and/or 20 micromol/L of AS I were significantly enhanced, and levels of TGF-beta1 mRNA, collagen IV and laminin were statistically decreased. By flowcytomery, percentages of S phase of cells incubated in high glucose and H2O2 were lowered, while those in AS I were increased. Furthermore, the physical behaviors of rats treated with 12 mg/kg of AS I restored with vigor and weight gaining, while the level of HbAlC was significantly reduced. Thus, AS I has antioxidative effects and is a potential compound worth further study because it may prevent the development of DN.
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PMID:The antioxidative effects of astragalus saponin I protect against development of early diabetic nephropathy. 1676 54


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