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

We examined the effect of two endogenous antioxidant agents, taurine and vitamin E, on renal function in experimental diabetes. Male Sprague-Dawley rats, rendered diabetic with streptozocin (STZ), were assigned to one of the following groups: 1) untreated; 2) insulin treatment with 6 U Ultralente insulin/day in two doses; 3) taurine supplementation by 1% taurine in drinking water; and 4) vitamin E supplementation at 100 IU vitamin E/kg chow. Animals were kept for 52 wk. The survival rate was similar (70-90%) in all groups except vitamin E-treated animals, of which 84% died by 6 mo. At 52 wk, glomerular filtration rate was elevated in untreated and taurine-treated STZ rats compared with normal or insulin-treated diabetic rats. Taurine supplementation reduced total proteinuria and albuminuria by nearly 50%. This treatment also prevented glomerular hypertrophy, preserved immunohistochemical staining for type IV collagen in glomeruli, and diminished glomerulosclerosis and tubulointerstitial fibrosis in diabetic animals. The changes in renal function and structure in taurine-treated diabetic rats were associated with normalization of renal cortical malondialdehyde content, lowering of serum free Fe2+ concentration, and decreased formation of the advanced glycooxidation products, pentosidine, and fluorescence in skin collagen. Administration of the vitamin E-enriched diet exacerbated the nephropathy in STZ-diabetic rats. In addition, vitamin E supplementation increased serum free Fe2+ concentration, enhanced renal lipid peroxidation, and accelerated the accumulation of advanced glycosylation end products (AGEs) in skin collagen. We conclude that administration of taurine, but not vitamin E, to rats with STZ-diabetes ameliorates diabetic nephropathy. The beneficial effect of taurine is related to reduced renal oxidant injury with decreased lipid peroxidation and less accumulation of AGEs within the kidney.
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PMID:Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats. 757 92

High glucose directly promotes lipid peroxidation and stimulates collagen production by cultured mesangial cells. We conducted the following experiments to ascertain whether vitamin E, a lipophilic antioxidant agent, could reverse these effects in vitro. Rat mesangial cells were grown to confluence and then maintained for 7 additional days in control media (DME) containing 5.6 mM glucose or experimental media containing 33.3 mM glucose. The test condition resulted in a near doubling of mesangial cell lipid peroxidation, assessed by measuring the content of conjugated dienes. High-glucose media also enhanced collagen production by 28% above the basal level in control media. Addition of vitamin E (100 microM) reversed both effects of the elevated ambient glucose level and prevented lipid peroxidation and normalized collagen production in cultured mesangial cells. These findings suggest that vitamin E functions as an endogenous antioxidant agent in the kidney to limit the development of glomerulosclerosis in diabetic nephropathy.
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PMID:Vitamin E prevents glucose-induced lipid peroxidation and increased collagen production in cultured rat mesangial cells. 802 21

High glucose and elevated levels of advanced glycosylation end products (AGEs) exert an antiproliferative effect on cultured mesangial cells. In view of the role of oxygen free radicals in the pathogenesis of diabetic nephropathy, we tested whether two endogenous antioxidants, taurine and vitamin E, ameliorate the effects of an elevated ambient glucose and/or AGEs on mesangial cell growth in vitro. Regardless of whether cell proliferation was assayed by the incorporation of [3H]thymidine, direct cell counting or bromodeoxyuridine (BrdU) cell staining, both taurine and vitamin E reversed the inhibitory effect of high glucose and AGEs on mesangial cell growth. In conjunction with our previous studies indicating that taurine and vitamin E reduce collagen production in mesangial cells exposed to high glucose, these findings suggest that endogenous antioxidants attenuate diabetic glomerulosclerosis by interfering with the bioactivation of transforming growth factor-6.
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PMID:Antioxidants reverse the antiproliferative effect of high glucose and advanced glycosylation end products in cultured rat mesangial cells. 812 33

Hyperglycemia directly contributes to the development of diabetic nephropathy. A high-serum glucose concentration alters intraglomerular hemodynamics and promotes deposition of extracellular matrix in the kidney. Nitric oxide (NO) is a short-lived messenger molecule that participates in the regulation of renal blood flow, GFR, and mesangial matrix accumulation. Therefore, in this study it was tested whether high glucose directly modulates NO synthesis by rat mesangial cells in vitro by measuring the accumulation of nitrite, the stable metabolite of NO, in the incubation media. Raising the external glucose concentration to 33.3 mM for 24 to 72 h reduced nitrite levels in cell supernatants in a time-dependent manner to a nadir of 14 +/- 3% of the amount in normal glucose media (5.6 mM) (P < 0.01). The decline in NO synthesis in high glucose media was paralleled by decreased cyclic guanosine monophosphate generation; however, there was no alteration in rat mesangial cell expression of inducible NO synthase protein. The suppressive effect of high glucose on NO production by mesangial cells was not modified by inhibition of protein kinase C (H-7), the addition of antioxidants (vitamin E or superoxide dismutase), or a pan-specific anti-transforming growth factor-beta antibody. An elevated ambient glucose caused a time-dependent reduction in mesangial cell L-arginine content. Addition of L-arginine (10 to 20 mM) to external media partially reversed the inhibitory effect of high glucose on mesangial cell NO production in a dose-dependent manner. The highest dose of L-arginine (20 mM) increased mesangial cell L-arginine content to comparable levels in normal and high glucose media. These results indicate that high glucose causes depletion of L-arginine in mesangial cells and compromises NO synthesis. Limitation in the metabolic precursor and other, as yet unidentified, factors act to reduce NO production by mesangial cells in the presence of an elevated ambient glucose level, a change that may play a role in the development of diabetic glomerulosclerosis.
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PMID:High glucose inhibits nitric oxide production in cultured rat mesangial cells. 925 54

The Heart Outcomes Prevention Evaluation (HOPE) study found that the ACE inhibitor ramipril can lower the risk of atherosclerotic disease events and death in patients without heart failure but with known atherosclerosis or with diabetes plus at least one cardiovascular risk factor. This benefit was independent of ramipril's effect on blood pressure. Additional benefits were a reduced risk of diabetic nephropathy in diabetic patients, and a lower likelihood of newly diagnosed diabetes. On the other hand, vitamin E in the doses and duration studied (400 IU/day for 4.5 years) did not lower risk significantly.
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PMID:The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not. 1078 Jan 1

Diabetes mellitus is characterized by complications affecting several organs, including the kidney. Lipid peroxidation increases in diabetes and has been implicated in the pathogenesis of diabetic complications. In this study, we examined the ability of two antioxidants, vitamin E and probucol, to reduce lipid peroxidation in vivo and renal hypertrophy, an early stage of diabetic nephropathy, in rats. Animals were divided into four groups: non-diabetic, diabetic, diabetic treated with vitamin E, and diabetic treated with probucol. Animals were given antioxidants by intraperitoneal injection after induction of diabetes by streptozotocin injection. After 7 wk, lipid peroxidation in vivo was measured by analyzing urinary excretion of lipophilic aldehydes and related carbonyl compounds (LACC) as 2,4-dinitrophenylhydrazones by high-performance liquid chromatography. A number of urinary lipophilic nonpolar and polar aldehydes and related carbonyl compounds were identified, almost all of which increased in diabetes. Antioxidant treatment resulted in significantly decreased excretion of urinary LACC excretion. Antioxidant treatment of diabetic rats reduced renal hypertrophy. There was a high correlation between kidney weight and urinary LACC. Since LACC are accepted markers of lipid peroxidation, these results indicate that antioxidants can reduce the elevated lipid peroxidation of diabetes and may slow the onset of diabetic nephropathy.
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PMID:Vitamin E and probucol reduce urinary lipophilic aldehydes and renal enlargement in streptozotocin-induced diabetic rats. 1113 82

Vitamin E treatment has been found to be beneficial in preventing or reducing diabetic nephropathy. Increased tissue calcium and abnormal microsomal Ca(2+)-ATPase activity have been suggested as contributing factors in the development of diabetic nephropathy. This study was undertaken to test the hypothesis that vitamin E reduces lipid peroxidation and can prevent the abnormalities in microsomal Ca(2+)-ATPase activity and calcium levels in kidney of streptozotocin (STZ)-induced diabetic rats. Male rats were rendered diabetic by a single STZ injection (55 mg x kg(-1) i.p.). After diabetes was verified, diabetic and age-matched control rats were untreated or treated with vitamin E (400-500 IU kg(-1) x day(-1), orally) for 10 weeks. Ca(2+)-ATPase activity and lipid peroxidation (MDA) were determined spectrophotometrically. Blood glucose levels increased approximately five-fold (> 500 mg x dl(-1)) in untreated-diabetic rats but decreased to 340+/-27 mg x dl(-1) in the vitamin E treated-diabetic group. Kidney MDA levels did not significantly change in the diabetic state. However, vitamin E treatment markedly inhibited MDA levels in both control and diabetic animals. Ca(2+)-ATPase activity was 0.483+/-0.008 U l(-1) in the control group and significantly increased to 0.754+/-0.010 U l(-1) in the STZ-diabetic group (p < 0.001). Vitamin E treatment completely prevented the diabetes-induced increase in Ca(2+)-ATPase activity (0.307+/-0.025 U l(-1), p < 0.001) and also reduced the enzyme activity in normal control rats. STZ-diabetes resulted in approximately two-fold increase in total calcium content of kidney. Vitamin E treatment led to a significant reduction in kidney calcium levels of both control and diabetic animals (p < 0.001). Thus, vitamin E treatment can lower blood glucose and lipid peroxidation, which in turn prevents the abnormalities in kidney calcium metabolism of diabetic rats. This study describes a potential biochemical mechanism by which vitamin E supplementation may delay or inhibit the development of cellular damage and nephropathy in diabetes.
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PMID:Effects of vitamin E on microsomal Ca(2+) -ATPase activity and calcium levels in streptozotocin-induced diabetic rat kidney. 1273 8

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

Pathogenesis of diabetic nephropathy, which belongs to most serious microangiopathic complications of diabetes, is still not completely clear. Thromboxan A2 and increased oxidation stress are new factors apparently associated with pathogenesis of diabetic nephropathy. It was the aim of the contribution to verify the participation of thromboxan A2 and oxidation stress in the pathogenesis of diabetic nephropathy, as well as to follow the effects of treatment with vitamin E on its progression. In 19 diabetic subjects with microalbuminemia (MA) (age 55.2 +/- 7.6 years), 10 diabetic subjects with normoalbuminemia (NA) (age 54.4 +/- 6.1 years) and in 10 healthy subjects (age 53.6 +/- 9.4) the authors examined the level of malondialdehyde (MLDA) in serum, metabolites of thromboxan A2 (thromboxan B2-TXB2) and prostacyclin PGI2 (6-keto-PGF1 alpha) in urine by means of an RIA method (Isotop, Hungary). The diabetic patients with microalbuminemia were subsequently administered natural vitamin E (EVIT, Rodisna, FRG) at the daily dose of 1200 IU for the period of four months. After two and four months, respectively, MA, MLDA, TXB2 and 6-keto-PGF1 alpha) were examined. The age of the subjects in the two groups was not significantly different. In diabetic subjects with MA, the authors observed significantly higher MLDA levels in serum than in the control individuals (0.55 +/- 0.26 vs. 0.22 +/- 0.02 mumol/l, P < 0.001) and a significant difference occurred also in TBX2 in urine (134.7 +/- 113.8 vs. 27.7 +/- 10.1 ng/12 h, P < 0.001). Increased levels of TXB2 in urine were already present in diabetic subjects with NA as compared with healthy individuals (69.1 +/- 38.8 vs. 27.7 +/- 10.1 ng/12 h, P < 0.05). The treatment with vitamin E caused a significant decrease of MA (93.8 +/- 45.6 vs. 67.95 +/- 28.4 micrograms/min, P < 0.05), MLDA in serum (0.55 +/- 0.26 vs. 0.32 +/- 0.16 mumol/l, P < 0.001). On the basis of our results it is possible to suppose the role of oxidation stress and increased level of thromboxan A2 in the pathogenesis of diabetic nephropathy. The authors also confirmed that the treatment with vitamin E favorably decreases microalbuminemia, while the nephroprotective effect is apparently mediated not only by the antioxidant action, but also the decrease of thromboxan A2 production.
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PMID:[Effect of vitamin E therapy on progression of diabetic nephropathy]. 1293 34

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


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