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)

The purpose of these studies was to determine how intravascular complement activation could lead to glomerular injury. Cobra venom factor (CVF) infused into the renal artery of rats resulted in increased excretion of protein in urine, which was maximal over the first 24 hours (51.2 +/- 6.0 mg/24 hours in CVF versus 14.1 +/- 0.9 mg/24 hours in saline-treated animals; P less than 0.001). Depletion of circulating neutrophils with anti-neutrophil serum significantly reduced the CVF-induced proteinuria in the first 24 hours (neutrophil depleted rats 22.7 +/- 2.8 mg/24 hours versus 63.4 +/- 9.9 mg/24 hours in neutrophil intact rats; P less than 0.005). Morphologic abnormalities (which were quantitated morphometrically) included accumulation of neutrophils in glomerular capillary loops, blebbing of endothelial cells, and epithelial cell foot process fusion. The increased protein excretion was reduced by 70% by simultaneous administration of catalase (23 +/- 4.3 mg/24 hours in CVF plus catalase versus 52.1 +/- 10 mg/24 hours in CVF alone; P less than 0.05). Catalase reduced glomerular endothelial cell blebbing and epithelial cell foot process fusion but not neutrophil accumulation in glomeruli as assessed by morphometry. In similar experiments superoxide dismutase, dimethyl sulfoxide, and deferoxamine did not prevent CVF-induced proteinuria. These studies, therefore, suggest that intravascular activation of complement in the rat causes glomerular injury and proteinuria which is dependent on neutrophils and upon the generation of hydrogen peroxide and/or its metabolites.
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PMID:Glomerular injury and proteinuria in rats after intrarenal injection of cobra venom factor. Evidence for the role of neutrophil-derived oxygen free radicals. 242 81

We examined the effect of the administration of different oxygen radical scavengers on the development of glomerulonephritis induced by cationic bovine gamma-globulin (cBGG). Treatment with the H2O2 scavenger catalase or the superoxide anion (O2-) scavenger superoxide dismutase (SOD) did not significantly reduce proteinuria. In contrast, treatment with the hydroxyl radical (OH.) scavengers dimethyl sulfoxide (DMSO) or dimethylthiourea resulted in significant decrements in proteinuria, from 156 +/- 20 mg/24 hours in saline solution--treated control rats to 70 +/- 17 mg/24 hours (p less than 0.05) and 37 +/- 10 mg/24 hours (p less than 0.01) in DMSO- and dimethylthiourea-treated rats, respectively. Therapy with DMSO for 5 days after induction of glomerular disease also resulted in amelioration of proteinuria, 10.0 +/- 5.0 mg/24 hours versus saline solution-treated rats, 67.6 +/- 16.2 mg/24 hours (p less than 0.005). OH. scavenger therapy did not influence glomerular morphology, glomerular immunoglobulin G (IgG), or complement deposition, or creatinine clearances of rats with glomerulonephritis. Furthermore, there were no significant differences in serum levels of C3 and C5 or anti-BGG antibody production between DMSO-treated rats and control rats. None of the radical scavengers administered altered the enhanced glomerular thromboxane synthesis characteristic of this model. Our results suggest that OH. generation mediates in part glomerular injury in cBGG-induced glomerulonephritis.
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PMID:Hydroxyl radical scavengers ameliorate proteinuria in rat immune complex glomerulonephritis. 246 May 71

The effect of 'scavengers' of reactive oxygen products (ROPs) was studied in the heterologous phase of anti-glomerular basement (anti-GBM) nephritis induced in rats. Glomerulonephritis was induced by the intravenous administration of sheep anti-GBM antibody (5 mg/100 g) to rats on day 0. The intraperitoneal administration of superoxide dismutase (SOD) 30 mg/kg/day or 150 mg/kg/day leads to a significant reduction in proteinuria on day 1 and also on day 3 in animals given SOD 30 mg/kg/day. Proteinuria was not significantly reduced by the intraperitoneal administration of inactivated SOD (150 mg/kg/day). In rats given polyethylene glycol coupled catalase (PEG-catalase) intraperitoneally at a dose of 10,000 iu/kg/day and 100,000 iu/kg/day proteinuria was lower than in rats with unmodified anti-GBM nephritis. These differences were significant on day 1 (P less than 0.05) in rats given PEG-catalase 100,000 iu/kg/day and on days 3 and 5 in rats treated with either dose of PEG-catalase (P less than 0.01). These data suggest a role for superoxide anion and hydrogen peroxide, or a product of their interaction such as hydroxyl radical, in glomerular injury induced by anti-GBM antibody.
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PMID:Reactive oxygen products in heterologous anti-glomerular basement membrane nephritis in rats. 278 25

We examined the effect of scavengers of reactive oxygen metabolites on proteinuria in the passive Heymann nephritis model of membranous nephropathy. Passive Heymann nephritis was induced by a single intravenous injection of anti-Fx1A IgG in a dose of 10 mg/100 g body weight. Superoxide dismutase, a scavenger of superoxide or catalase which destroys hydrogen peroxide, did not affect the proteinuria. In contrast, dimethylthiourea (DMTU, 500 mg/kg followed by 125 mg/kg ip twice a day), a scavenger of hydroxyl radical, markedly reduced the proteinuria (day 5: anti-Fx1A 53 +/- 13, n = 18; anti-Fx1A + DMTU, 21 +/- 6 mg/24 h, n = 15, P less than 0.001). Experiments with 125I-labeled anti-Fx1A antibody demonstrated that DMTU did not affect the amount of antibody deposited in the kidney. Semiquantitative estimation of IgG and complement deposition in the kidney showed no differences between the DMTU-treated and control rats. A second hydroxyl radical scavenger, sodium benzoate (150 mg/kg ip twice a day), also resulted in marked reduction in proteinuria (day 5: anti-Fx1A 56 +/- 7, n = 9; anti-Fx1A + benzoate, 14 +/- 4 mg/24 h, n = 8, P less than 0.01). Because of the participation of iron in biological systems to generate hydroxyl radical, we also examined the effect of deferoxamine (DFO, 35 mg/day), an iron chelator, on the anti-Fx1A-induced proteinuria. There was a significant reduction in proteinuria in rats treated concurrently with DFO (day 5: anti-Fx1A 67 +/- 13, n = 15; anti-Fx1A + DFO, 29 +/- 4 mg/24 h, n = 15, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence suggesting a role for hydroxyl radical in passive Heymann nephritis in rats. 283 37

The cellular processes responsible for the proteinuria induced by the aminonucleoside of puromycin (PA) remain inadequately defined. Hypoxanthine is both a metabolic breakdown product of PA as well as a substrate for xanthine oxidase, which catalyzes its enzymatic conversion to xanthine and uric acid, yielding the superoxide anion in the process. We examined whether oxygen free radical production contributes to the development of proteinuria in this model. Seven groups of male Sprague-Dawley rats were studied. Proteinuria was quantitated and histology examined 7 days after rats were treated with PA intravenously over 5 min. PA-treated animals received either saline, dimethyl sulfoxide, superoxide dismutase, or catalase over 30 min prior to and 30 min following PA administration. Another group received allopurinol over 4 hr prior to PA. The superoxide dismutase and allopurinol treatment groups had a significant suppression of urinary protein excretion compared to the PA control group. There were also less severe glomerular morphologic changes in the superoxide dismutase group vs. the PA controls, which demonstrated a pathologic pattern that included epithelial cell blebbing, segmental mesangial cell proliferation and matrix expansion, loss of glomerular capillary lumina, and occasional adhesions between the glomerular tuft and Bowman's capsule. The allopurinol group exhibited normal glomerular morphology on light microscopy, with the exception of occasional epithelial cell blebs. All groups showed spreading of the epithelial cell cytoplasm along the glomerular basement membrane with loss of foot processes, focal areas of lifting of the epithelial cell from the glomerular basement membrane, cytoplasmic vacuolization, and protein reabsorption droplets; however, allopurinol-treated animals demonstrated these changes to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A role for oxygen free radicals in aminonucleoside nephrosis. 370 6

Phorbol myristate acetate (PMA) is known to be a potent activator of neutrophils and macrophages resulting in the generation of large amounts of oxygen-free radicals by these cells. When injected into the left renal artery of 250 to 300 g male Sprague-Dawley rats, PMA caused significant proteinuria compared to control rats which received normal saline (35.4 +/- 4 mg/24 hr in PMA treated vs. 14.1 +/- 0.9 mg/24 hr in saline control, P less than 0.02). The proteinuria was associated with evidence of glomerular injury. These PMA-induced alterations were not prevented by complement depletion but were prevented by prior depletion of neutrophils. The coinstillation of catalase prevented the development of the proteinuria (catalase + PMA 12.7 +/- 2.3 mg/24 hr vs. PMA alone 38.2 +/- 5.7 mg/24 hr, P less than 0.001) suggesting that H2O2 and/or its metabolites derived from neutrophils were important in the PMA-induced proteinuria. In contrast, superoxide dismutase (SOD) had no effect. We conclude that, following the intra-arterial injection of PMA, neutrophil-derived hydrogen peroxide and/or its metabolic products are capable of causing acute proteinuria in association with morphological alterations in glomeruli of rats.
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PMID:Role of oxygen radicals in phorbol myristate acetate-induced glomerular injury. 399 39

Patients with minimal change nephrotic syndrome (MCNS) frequently have suppressed in vivo and in vitro immune responsiveness of uncertain etiology. Because increased suppressor cell activity has been associated with this disease, urines from MCNS patients were screened for activity of the lymphokine soluble immune response suppressor (SIRS), a product of concanavalin A- or interferon-activated suppressor T cells. Urines from untreated MCNS patients suppressed polyclonal plaque-forming cell responses of cultured splenocytes. This suppressive activity was identified as human SIRS by the following functional and physical criteria: molecular weight estimated by gel filtration; kinetics of suppression; inhibition of suppression by catalase, levamisole, and 2-mercaptoethanol; abrogation of activity by acid or protease treatment; elution pattern on high performance liquid chromatography; and cross-reactivity with monoclonal antimurine SIRS antibodies. Suppressive activity disappeared from urine after initiation of treatment but before remission of symptoms. Urines were tested from 11 patients with MCNS, all of whom excreted SIRS. In addition, two nephrotic patients with acute glomerulonephritis and three nephrotic patients with membranoproliferative disease excreted SIRS, but other nephrotics and all nonnephrotic patients did not. These results indicate that excretion of SIRS occurs in certain cases of nephrotic syndrome and that the presence of SIRS in the urine is not accounted for solely by the presence of proteinuria or nephrosis. Serum from four nephrotic patients also contained SIRS, whereas neither serum nor urine from six normal subjects contained SIRS activity. The systemic presence of SIRS in these four patients, and the identification of SIRS in urines from a larger group of patients, suggest a possible role for SIRS in the suppressed immune responses often found in nephrotic syndrome.
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PMID:Identification of the lymphokine soluble immune response suppressor in urine of nephrotic children. 401 84

Previously we have demonstrated that systemic activation of the complement system after intravenous injection of cobra venom factor (CVF) results in acute lung injury as reflected by increases in the vascular permeability of the lung as well as by morphologic evidence of damage to lung vascular endothelial cells. In using the vascular permeability of the lung as the reference, the current studies show a quantitative correlation between lung injury and the appearance in plasma of lipid peroxidation products (conjugated dienes) as well as increased concentrations of lactic dehydrogenase (LDH) and one of its isoenzymes (LDH-4). After injection of CVF, extracts of lungs also showed elevated levels of conjugated dienes, whereas no elevations were found in extracts of liver, kidney, and spleen. There was no evidence in CVF-injected rats of renal or hepatic injury as reflected by the lack of development of proteinuria and the failure to detect increased serum levels of liver-related enzymes. Other peroxidation products identified in plasma of CVF-injected rats involved hydroperoxides and fluorescent compounds with features of Schiff bases. Not surprisingly, malondialdehyde was not found to be a reliable plasma indicator of lipid peroxidation associated with oxygen radical-mediated lung vascular injury. In using a model of oxygen radical-independent lung injury induced by oleic acid, although large amounts of LDH and LDH-4 were found in the plasma, no increases in plasma levels of conjugated dienes were detected. In CVF-injected animals treated with interventions protective against lung injury (neutrophil depletion, catalase, hydroxyl radical scavengers, or iron chelators), there were striking reductions in the plasma levels of conjugated dienes, hydroperoxides, and fluorochromic products. Morphometric analysis of lung sections revealed that the protective interventions did not interfere with the accumulation of neutrophils in lung interstitial capillaries after systemic activation of complement. In vitro studies with phorbol-stimulated neutrophils failed to demonstrate appearance of conjugated dienes, suggesting that the dienes appearing in plasma of CVF-injected animals are not the result of autotoxic changes in neutrophils. The data presented in this paper suggest that acute lung injury mediated by oxygen radicals derived from phagocytic cells can be monitored by the appearance in plasma of products of lipid peroxidation.
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PMID:Systemic complement activation, lung injury, and products of lipid peroxidation. 403 Oct 60

The altered functional properties of the glomerular capillary wall in a model of autologous immune complex disease (Heymann's nephritis) was studied by electron microscopy using intravenously injected protein tracers of varying molecular weight. There was an increase in the permeability of the glomerular basement membrane (GBM) itself to large molecules; this change was focal and was found in those areas where the GBM contained immune complex deposits. Both ferritin and catalase, tracers normally restricted from passing the glomerular filter, were present in the urinary space within minutes of injection. No evidence was obtained for increased glomerular epithelial transport in this disease. Foot process swelling and "close" junction formation was moderate, even in animals with marked degrees of proteinuria. Indirect evidence, therefore, makes an alteration in the slit pore complex likely. In addition, there was immediate and selective concentration of all tracers within deposits, though ferritin was partially excluded from some deposits. This phenomenon may be of significance in the perpetuation of the disease.
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PMID:Altered functional properties of the renal glomerulus in autologous immune complex nephritis: an ultrastructural tracer study. 413 94

Acute glomerular injury in the rat has been induced by the intrarenal, intraarterial infusion of sheep antibody to glomerular basement membrane (antiglomerular basement membrane). The antiglomerular basement membrane antibody has been verified to be of the variety that is complement and neutrophil dependent for the induction of acute proteinuria, which peaks during the first 24 hours. Following injection of the antibody, acute, intense, glomerular injury resulted, with the denuding of glomerular vascular basement membrane associated with extensive damage or destruction of glomerular endothelial cells and fusion of epithelial cell foot processes. Treatment of animals with catalase produced, in a dose-dependent manner, as much as 75% protection against glomerular injury, as assessed by reduction in the proteinuria. Treatment of animals with superoxide dismutase caused a small reduction in the degree of glomerular injury, again assessed by a reduction in proteinuria. However, this protective effect of superoxide dismutase was not found to be statistically significant. The hydroxyl radical scavenger, dimethyl sulfoxide, which has been shown to protect against endothelial cell injury following systemic activation of complement, was not protective in the anti-GBM model. Morphologically, glomeruli from catalase-protected rats showed numerous neutrophils but little or no evidence of injury of either glomerular endothelial or epithelial cells. These data suggest that acute glomerular injury produced by antiglomerular basement membrane is related to H2O2 production from activated neutrophils.
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PMID:Evidence for the role of oxygen radicals in acute nephrotoxic nephritis. 609 Aug 9


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