Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selenium (Se) deficiency reduces glutathione peroxidase (GPx) activity, resulting in increased oxidative stress. We examined how Se deficiency induces renal injury via oxidative stress over time during the Se-deficient period. Seventy-two male Wistar rats were divided into two groups and fed either a control or Se-deficient diet. Rats were sacrificed on weeks 1, 2, 4, 6, 9, and 12. Blood and urine samples were collected, and the kidneys were removed. Urinalysis was performed, and creatinine clearance (Ccr) was calculated. Expressions of cellular GPx (cGPx) and phospholipid hydroperoxidase GPx (PHGPx) mRNA and GPx activity were measured. Histology was evaluated by light microscopy with immunohistochemistry for 4-hydroxy-2-nonenal (HNE) and vimentin. The Se-deficient diet caused significant decreases in GPx activity and cGPx mRNA expression but no change in PHGPx mRNA, together with significant proteinuria and glucosuria and slight decline in Ccr. The Se-deficient diet induced calcification in the kidney and increased the distribution of HNE and vimentin immunostaining in proximal tubuli, particularly around the outer medulla stripe. However, the histological damage did not progress after 6 weeks of deficiency. Se deficiency induces proteinuria and glucosuria with renal calcification, which may be primarily induced by injury of proximal tubuli via oxidative stress.
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PMID:Effect of selenium-deficient diet on tubular epithelium in normal rats. 1710 41

It has been suggested that oxidative stress is involved in d-serine-induced nephrotoxicity. The purpose of this study was to assess if oxidative stress is involved in this experimental model using several approaches including (a) the determination of several markers of oxidative stress and the activity of some antioxidant enzymes in kidney and (b) the use of compounds with antioxidant or prooxidant effects. Rats were sacrificed at several periods of time (from 3 to 24h) after a single i.p. injection of d-serine (400mg/kg). Control rats were injected with l-serine (400mg/kg) and sacrificed 24h after. The following markers were used to assess the temporal aspects of renal damage: (a) urea nitrogen (BUN) and creatinine in blood serum, (b) kidney injury molecule (KIM-1) mRNA levels, and (c) tubular necrotic damage. In addition, creatinine clearance, proteinuria, and urinary excretion of N-acetyl-beta-d-glucosaminidase (NAG) were measured 24h after d-serine injection. Protein carbonyl content, malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), fluorescent products of lipid peroxidation, reactive oxygen species (ROS), glutathione (GSH) content, and heme oxygenase-1 (HO-1) expression were measured as markers of oxidative stress in the kidney. Additional experiments were performed using the following compounds with antioxidant or pro-oxidant effects before d-serine injection: (a) alpha-phenyl-tert-butyl-nitrone (PBN), a spin trapping agent; (b) 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron(III) (FeTPPS), a soluble complex able to metabolize peroxynitrite; (c) aminotriazole (ATZ), a catalase (CAT) inhibitor; (d) stannous chloride (SnCl(2)), an HO-1 inductor; (e) tin mesoporphyrin (SnMP), an HO inhibitor. In the time-course study, serum creatinine and BUN increased significantly on 15-24 and 20-24h, respectively, and KIM-1 mRNA levels increased significantly on 6-24h. Histological analyses revealed tubular necrosis at 12h. The activity of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase remained unchanged at all times studied. Protein carbonyl content, MDA, 4-HNE, and ROS remained unchanged at all time-points studied. GSH content decreased transiently on 9 and 12h. Interestingly, fluorescent products of lipid peroxidation decreased significantly on 3-24h. HO-1 expression was undetectable by Western blot and the immunohistochemistry studies revealed that the intensity of HO-1 staining was weak. The administration of PBN, FeTPPS, ATZ, SnCl(2), and SnMP did not prevent or enhance renal damage induced by d-serine. Our data taken as a whole suggest that oxidative stress is not involved in the early phase of the nephrotoxicity induced by d-serine.
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PMID:Evaluation of oxidative stress in D-serine induced nephrotoxicity. 1711 13

Accumulation of plasma advanced oxidation protein products (AOPP) has been found in patients with chronic kidney disease. However, the biologic consequences of AOPP consumption on progression of renal disease still are unclear. For testing of the hypothesis that AOPP accelerate progression of chronic kidney disease, Sprague-Dawley rats were subjected to five-sixths nephrectomy (5/6 Nx) or to sham operation. Rats in each group were randomly assigned in three subgroups (n = 30 in each group) and treated with repeated intravenous injections of AOPP-modified rat serum albumin (RSA), unmodified RSA, or vehicle for indicated period. Compared with RSA- or vehicle-treated 5/6 Nx rats, AOPP RSA-treated 5/6 Nx rats displayed greater proteinuria, higher serum creatinine, and lower creatinine clearance. AOPP challenge resulted in more renal hypertrophy, higher macrophage influx, and greater renal fibrosis in the remnant kidney. Chronic administration of AOPP in sham-operated rats increased urinary protein excretion and renal macrophage infiltration, but histologic renal fibrosis was not observed during the study period. AOPP treatment enhanced AOPP level in renal tissue. This was associated with marked increase of thiobarbituric acid reactive substances, decrease of glutathione peroxidase activity, and upregulated expression of monocyte chemoattractant protein-1 and TGF-beta1 in renal cortex. These data indicate that AOPP might be a new and potentially important mediator of renal fibrosis in the remnant kidney. Chronic accumulation of AOPP promotes renal fibrosis probably via a redox-sensitive inflammatory pathway.
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PMID:Advanced oxidation protein products accelerate renal fibrosis in a remnant kidney model. 1720 14

Diet-derived advanced glycation end products (AGEs) contribute significantly to accumulation of AGEs in renal insufficiency. To test whether modulation of dietary AGEs would impact on progression of chronic renal disease, 5/6 nephrectomy rats were randomly placed on three diets that differed only in AGEs content (low AGEs diet (LAD), high AGEs diet (HAD), and standard rodent diet (SRD)) for 5-13 weeks. Compared with SRD- or HAD-fed rats, LAD-treated animals showed decreased proteinuria and retarded decline of creatinine clearance without alteration of blood pressure. Glomerular volume was reduced by 23% compared with HAD-fed rats at week 13 (P<0.001). Renal fibrosis progressed with time in the remnant kidneys from HAD-fed rats. However, LAD-fed animals presented a better-preserved structure of the kidneys. LAD-fed rats demonstrated significantly decreased serum and renal AGEs concentration (P<0.01 and P<0.01). This was associated with marked decrease of intrarenal advanced oxidation protein products and thiobarbituric acid reactive substances, as well as increase of glutathione peroxidase activity. LAD treatment also downregulated expression of monocyte chemoattractant protein-1 and transforming growth factor-1 and ameliorated macrophage infiltration in the remnant kidney. These results demonstrated that restriction of dietary AGEs intake retards progression of renal fibrosis and dysfunction in the remnant kidney model.
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PMID:Restricted intake of dietary advanced glycation end products retards renal progression in the remnant kidney model. 1734 81

Potassium dichromate (K(2)Cr(2)O(7))-induced nephrotoxicity is associated with oxidative stress. In the present work the effect of garlic powder, a recognized antioxidant, on K(2)Cr(2)O(7)-induced nephrotoxicity and oxidative stress was studied. Rats were fed a 2% garlic powder diet for 1 month. A single injection of K(2)Cr(2)O(7) (15 mg/kg) to rats induced tubule interstitial damage and an increase in the following markers of renal injury 2 days later: blood urea nitrogen (4.6-fold), serum creatinine (9.7-fold), proteinuria (35.9-fold), urinary excretion of N-acetyl-beta-d-glucosaminidase (12.9-fold) and glutathione-S-transferase (2.3-fold) and a decrease of 65% in serum glutathione peroxidase activity. In addition, K(2)Cr(2)O(7) injection increased the following nitrosative and oxidative stress markers in kidney: 3-nitrotyrosine (1.9-fold), 4-hydroxy-2-nonenal (2.1-fold), malondialdehyde (1.8-fold) and protein carbonyl content (1.7-fold). It was found that garlic powder feeding was able to prevent by 44-71% the alterations in the markers of renal injury studied, by 55% the histological damage, and by 47-100% the increase in markers of oxidative and nitrosative stress. It is concluded that the ability of garlic powder to ameliorate K(2)Cr(2)O(7)-induced renal injury is associated with its antioxidant properties. Our data support the use of garlic powder as a renoprotective agent.
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PMID:Protective effects of garlic powder against potassium dichromate-induced oxidative stress and nephrotoxicity. 1795 May 12

Larrea tridentata also known as Creosote bush, Larrea, chaparral, greasewood or gobernadora has been used in the folk medicine for the treatment of several illnesses. The primary product that is present at high concentrations in the leaves from this plant is nordihydroguaiaretic acid (NDGA) which is a powerful antioxidant. On the other hand, potassium dichromate (K(2)Cr(2)O(7))-induced nephrotoxicity is associated with oxidative stress. The aim of this work was to study the effect of NDGA on K(2)Cr(2)O(7)-induced nephrotoxicity and oxidative stress. Nephrotoxicity was induced by a single injection of K(2)Cr(2)O(7) (15 mg/Kg). A group of K(2)Cr(2)O(7)-treated rats was administered NDGA by mini osmotic pumps (17 mg/Kg/day). The results show that NDGA was able to ameliorate the structural and functional renal damage evaluated by histopathological analysis and by measuring proteinuria, urinary excretion of N-acetyl-beta-d-glucosaminidase, serum creatinine, and serum glutathione peroxidase activity. In addition, immunostaining of 4-hydroxy-2-nonenal and 3-nitrotyrosine, markers of oxidative and nitrosative stress, respectively, was ameliorated by the NDGA treatment. These data strongly suggest that the antioxidant properties of NDGA are involved in its renoprotective effect in K(2)Cr(2)O(7)-treated rats.
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PMID:Nordihydroguaiaretic acid attenuates potassium dichromate-induced oxidative stress and nephrotoxicity. 1815 43

Gentamicin (GM), an antibiotic against life threatening bacterial infection, induces remarkable toxicity in the kidney. Histological studies have indicated that mitochondria, microsomes, lysosomes and plasma membranes of renal proximal convoluted tubules in particular are major GM targets. Despite numerous investigations, the biochemical/cellular basis of GM nephrotoxicity is not well understood. Recently reactive oxygen species (ROS) are considered to be important mediators of GM-induced nephrotoxicity. We hypothesize that GM causes damage to intracellular organelles and affects their structural integrity and alters metabolic and other functional capabilities. To address above hypothesis a long-term, time-dependent effect of GM has been studied on blood/urine parameters, enzymes of carbohydrate metabolism, brush border membrane (BBM) and basolateral (BLM), lysosomes and oxidative stress in renal tissues. A nephrotoxic dose of GM (80 mg/kg body weight) was administered to rats daily for 15 days. The long-term treatment with GM induced a significant increase in serum creatinine, blood urea nitrogen followed by massive proteinuria, glucosuria, enzymuria along with loss of electrolytes in the urine. The activities of the enzymes of carbohydrate metabolism, plasma membranes, lysosomes significantly declined. The activities of antioxidant enzymes e.g. superoxide dismutase, catalase and glutathione peroxidase were severely depressed and lipid peroxidation was significantly increased in the renal cortex and medulla. We conclude that GM administration induced oxidative damage to renal tissues that resulted in impaired carbohydrate metabolism and decreased activities of BBM, BLM and lysosomes associated with increased lipid peroxides.
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PMID:Time dependent effects of gentamicin on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in rat kidney tissues. 1820 28

The present study was intended to appraise the oxidant and antioxidant status in preeclampsia women. Seventy-seven preeclampsia women with severe variety having average B.P. of 170/140 mmHg with proteinuria; 47 preeclampsia women with mild variety having average B.P. of 138/100 mmHg were compared to 56 healthy pregnant women and 15 non-pregnant women for oxidant and antioxidant status. Lipid peroxidation was assessed by measuring malondialdehyde (MDA), and antioxidant status was assessed by measuring antioxidant enzymes N.B.; superoxide dismutase (SOD), glutathione peroxidase, catalase and vitamins viz; A, E, C and reduced glutathione (GSH). Lipid peroxidation was significantly higher in severe preeclampsia women. Antioxidant status was also compromised as is evident from decreased GSH levels and increased SOD activities not only in severe preeclampsia but also in normal pregnancy and mild preeclampsia women compared to non-pregnant women. Decreased antioxidant enzyme activity viz catalase and glutathione peroxidase was observed in pregnancy as compared to non-pregnant women. The levels of vitamin E which act as an antioxidant were significantly elevated in preeclampsia compared to that of normal pregnancy. These findings conclude that initially the oxidative stress due to pregnancy-induced hypertension is critically combated by the intricate defensive mechanism of natural antioxidant system of the body. It appears that this imbalance between oxidant and antioxidant is the effect of disease and not the causative factor.
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PMID:Alterations in lipid peroxidation and antioxidant status in pregnancy with preeclampsia. 1837 68

Intrauterine and postnatal zinc restriction may result in an adverse environment for the development of cardiovascular and renal systems. This study evaluated the effects of moderate zinc deficiency during fetal life, lactation, and/or postweaning growth on systolic blood pressure, renal function, and morphology in adult life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy up to weaning. After weaning, male offspring of each group of mothers were fed low or control zinc diet. Systolic blood pressure, creatinine clearance, proteinuria, renal morphology, renal apoptosis. and renal oxidative stress state were evaluated after 60 days. Zinc deficiency during pre- and postweaning growth induced an increase in systolic blood pressure and a decrease in the glomerular filtration rate associated with a reduction in the number and size of nephrons. Activation of renal apoptosis, reduction in catalase activity, glutathione peroxidase activity, and glutathione levels and increase in lipid peroxidation end products could explain these morphometric changes. Zinc deficiency through pre- and postweaning growth induced more pronounced renal alteration than postweaning zinc deficiency. These animals showed signs of renal fibrosis, proteinuria, increased renal apoptosis, and higher lipid peroxidation end products. A control diet during postweaning growth did not totally overcome renal oxidative stress damage, apoptosis, and fibrosis induced by zinc deficiency before weaning. In conclusion, zinc deficiency during a critical period of renal development and maturation could induce functional and morphological alterations that result in elevated blood pressure and renal dysfunction in adult life.
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PMID:Moderate zinc restriction during fetal and postnatal growth of rats: effects on adult arterial blood pressure and kidney. 1852 16

We evaluated whether the blockade of the proinflammatory transcription factor NF-kappaB would modify the oxidative stress, inflammation, and structural and hemodynamic alterations found in the kidney as a result of massive proteinuria. Twenty male Sprague-Dawley rats were injected with 2 g of BSA intraperitoneally daily for 2 wk. Ten of them received in addition the inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate (PDTC; 200 mg.kg(-1).day(-1) sc) and the rest received vehicle. Seven rats that received intraperitoneal saline were used as controls. Glomerular hemodynamics were studied after 14 days. Markers of oxidative stress (NF-kappaB subunit p65+ cells, 3-nitrotyrosine, and 4-hydroxynonenal), inflammation (cortical CD68+ cells and NOS-II), and afferent arteriole damage were assessed by immunohistochemistry and morphometry. Activity of antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase was evaluated in renal cortex and medulla. Albumin overload induced massive proteinuria, oxidative stress with reduced activity of antioxidant enzymes, NF-kappaB activation, inflammatory cell infiltration, a significant presence of proteinaceous casts, systemic and glomerular hypertension, as well as arteriolar remodeling. Treatment with PDTC prevented or improved all of these findings. In this model of nephrotic syndrome, we demonstrate a key role for oxidative stress and inflammation in causing systemic and glomerular hypertension and proteinuria. Oxidative stress and inflammation may have a key role in accelerating renal injury associated with intense proteinuria.
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PMID:Treatment with pyrrolidine dithiocarbamate improves proteinuria, oxidative stress, and glomerular hypertension in overload proteinuria. 1875 1


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