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)

Role of reactive oxygen species (ROS) was studied in accelerated nephrotoxic nephritis (NTN) in rats. In this experimental model, histological examination, and luminol amplified chemiluminescence (CL) assay of peripheral polymorphonuclear neutrophils (PMN), peritoneal macrophages (M phi), and isolated glomeruli were performed time-sequentially. Effect of ROS scavengers were also examined in this experiment. Daily dosages of bovine liver catalase and SOD were 550,000 and 1,000 units respectively. After nephrotoxic IgG injection, CL of glomeruli increased strikingly attaining peak at day 1, and remained high until the end of the experiment. This increase of CL may have reflected the release of ROS by glomerular cells and/or infiltrating cells stimulated in situ. In fact, peripheral PMN and peritoneal M phi showed no increase of CL after nephrotoxic IgG injection. Glomerular cells increased as early as 3 hours after induction of nephritis. Accumulation of PMN was noted for the first three days, whereas that of M phi became prominent after 4 days. Favourable effect was obtained in terms of proteinuria by administration of catalase, only when catalase was given at initial 3 days of nephritis. The data suggest that generation of ROS reflected by increase of CL in glomeruli of NTN rats is attributable to the PMN and M phi infiltrated in glomeruli as well as glomerular resident cells per se. It is also suggested that glomerular PMN increasing in the early phase of NTN plays a considerable role in glomerular injury.
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PMID:[Production of reactive oxygen species and scavenger treatment in nephrotoxic nephritis]. 147 15

We examined the effect of a selenium-deficient diet on two experimental models of glomerular disease, the puromycin aminonucleoside (PAN)-induced nephrotic syndrome, a model of minimal change disease, and passive Heymann nephritis, a complement-dependent and neutrophil-independent model that resembles membranous nephropathy. The specific activity of selenium-dependent glutathione peroxidase was markedly reduced in the liver, the kidney cortex, and in glomeruli in weanling male Sprague-Dawley rats placed on a selenium-deficient diet for 6 wk compared with rats fed a selenium-replete diet, with no significant differences in the specific activities of superoxide dismutase or catalase. PAN-injected selenium-deficient rats had a marked and significantly greater proteinuria throughout the course of the experiment compared with PAN-injected selenium-replete rats with no significant histological differences. In the passive Heymann nephritis model induced by injecting anti-Fx1A immunoglobulin G, rats fed a selenium-deficient diet had significantly higher urinary protein (day 5: 91 +/- 16 mg/24 h, n = 10) compared with rats fed a selenium-replete diet (52 +/- 5 mg/24 h, n = 11) with no differences in the amount of antibody deposited in the kidney. The most likely explanation for the effect of a selenium-deficient diet is that selenium deficiency resulted in a marked reduction of glutathione peroxidase, thus indicating an important role of glutathione peroxidase in these models of glomerular injury.
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PMID:Effect of selenium-deficient diet in experimental glomerular disease. 163 44

To identify the specific in vivo renal effect of reactive oxygen species (ROS), hydrogen peroxide (H2O2) was infused directly into the left renal artery in Munich-Wistar rats. H2O2 (5 to 50 mumol over 1 h) induced a dose-dependent increase in urine protein excretion rate in infused kidneys, reaching a maximum at the dose of 35 mumol (on average, a 60-fold increase from baseline). The H2O2 (35 mumol)-induced proteinuria peaked over 1 h and completely normalized by 24 h after the infusion. Electrophoresis revealed that the urine protein is primarily of glomerular origin. Fractional clearances of graded-size neutral dextran of larger molecular radii, an index of glomerular size selectivity, were significantly and substantially elevated immediately but normalized by 24 h after the infusion. GFR and RPF rate remained unchanged throughout the entire time course examined. The H2O2-induced proteinuria was largely prevented by pretreatment with catalase (20 mg, iv) or deferoxamine (30 mg/100 g body wt, iv). Thus, iron-dependent metabolites of hydrogen peroxide appear to be involved in this proteinuria and glomerular size-selective defect. Light and electron microscopy, including determination of anionic site density at lamina rara externa of glomerular capillary wall by polyethyleneimine staining, did not reveal any appreciable abnormality throughout the study period, including at the peak of proteinuria. Thus, ROS can cause massive, reversible proteinuria by inducing a molecular size-selectivity defect of the glomerular capillary wall without apparent ultrastructural abnormalities. The results raise the possibilities: (1) that persistent proteinuria of a variety of renal diseases may reflect persistence of pathogenic ROS acting on glomeruli because the potent proteinuric effect of ROS can be transient (2) that the light and electron microscopy abnormalities in glomeruli of ROS-induced renal injuries reported thus far may have no direct causal linkage to proteinuria; and, finally, (3) ROS-induced reversible proteinuria may relate to the mechanism of clinical functional proteinuria, which involves increased oxygen and ROS metabolism, e.g., exercise-induced proteinuria.
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PMID:Reactive oxygen metabolites cause massive, reversible proteinuria and glomerular sieving defect without apparent ultrastructural abnormality. 172 53

Hydrogen peroxide (H2O2) contributes to renal cellular injury. alpha-Keto acids nonenzymatically reduce H2O2 to water while undergoing decarboxylation at the 1-carbon (1-C) position. We examined, in vitro and in vivo, the protective role of sodium pyruvate in H2O2-induced renal injury. Pyruvate effectively scavenged H2O2 in vitro, and suppressed H2O2-induced renal lipid peroxidation. Injury to LLC-PK1 cells induced by hydrogen peroxide was attenuated by pyruvate to an extent comparable to that seen with catalase. Studies utilizing [1-14C]pyruvate further demonstrated 1-C decarboxylation concurrent with cytoprotection by pyruvate from H2O2-induced injury. Pyruvate was also protective in vivo. Infusion of pyruvate before and during the intrarenal infusion of H2O2 attenuated H2O2-induced proteinuria. Systemic administration of pyruvate was also protective in the glycerol model of acute renal failure, a model also characterized by increased generation of H2O2. These findings indicate that pyruvate, a ubiquitous alpha-keto acid, scavenges H2O2 and protects renal tissue in vitro and in vivo from H2O2-mediated injury. These data suggest a potential therapeutic role for pyruvate in diseases in which increased generation of H2O2 is incriminated in renal damage.
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PMID:Hydrogen peroxide-induced renal injury. A protective role for pyruvate in vitro and in vivo. 175 50

In order to study the role of active oxygen radicals on the progression of the immune-complex (IC) nephritis, we administered superoxide dismutase (SOD), catalase (CAT), and dimethylthiourea (DMTU) to (NZB x NZW) F1 mice from 8 weeks of age, 3 times a week. At 40 weeks of age, the urine protein of the control (n = 23) was 11.4 +/- 4.1 mg/day. SOD (n = 12), CAT (n = 6) and SOD + CAT (n = 5) groups were 1.5 +/- 0.4, 25.4 +/- 14.7, 0.7 +/- 0.1 mg/day, respectively. DMTU group (n = 12) showed significantly less proteinuria (0.6 +/- 0.1 mg/day, p less than 0.05) than control. Even if the injection was begun from the late stage of the disease, some effect was observed. Moreover, by DMTU, urinary excretion ratio of PGF1 alpha/TXB2 0.025 +/- 0.003 was higher than control 0.015 +/- 0.001 (p less than 0.05). These findings suggest that oxygen radicals may play an important role during the progression of lupus nephritis. Among the oxygen radical species, hydroxyl radical is considered to be the most pathogenetic factor in IC-mediated nephritis.
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PMID:[Role of active oxygen on the progression of murine lupus nephritis]. 190 63

In subcellular systems, doxorubicin hydrochloride (ADR) leads to the generation of reactive oxygen species such as superoxide anion. Because reactive oxygen species have been shown to be important mediators of glomerular injury in several animal models, we sought to determine whether reactive oxygen species play a significant role in the pathogenesis of ADR-induced nephrotic syndrome in the rat. Rats pretreated with a variety of free radical scavengers (superoxide dismutase conjugated to polyethylene glycol [PEGSOD], catalase, catalase plus PEGSOD, dimethylsulfoxide, desferoxamine, or n-acetyl cysteine) had no significant reduction in proteinuria at 3 weeks after ADR administration when compared with rats receiving ADR in the absence of scavengers. No evidence was seen of increased lipid peroxidation or depletion of reduced glutathione in renal cortex tissue obtained up to 24 hours after administration of ADR. No changes were seen in the renal cortical levels of either enzyme activity or immunoreactive protein for the endogenous antioxidant enzymes superoxide dismutase (either the Mn or CuZn forms) or catalase after ADR. Total and MnSOD activities in glomeruli isolated from rats after ADR administration fell significantly, though CuZnSOD activity was increased. The effect of ADR on cultured rat mesangial or epithelial cells was also evaluated. ADR inhibited growth of both cell types at concentrations of approximately 5 to 10 mumol/L, an order of magnitude below the reported Michaelis-Menten constant for ADR-induced superoxide production. The growth inhibitory effect could not be prevented in either cell type by treatment with PEGSOD, catalase, or PEGSOD plus catalase. This combination of results from in vivo and in vitro studies provides no evidence for an important role of reactive oxygen species in ADR nephrosis and suggests that other known mechanisms of ADR cytotoxicity, such as interference with DNA metabolism, mediate the glomerular injury.
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PMID:Evaluation of the role of reactive oxygen species in doxorubicin hydrochloride nephrosis. 194 May 84

We examined the effect of glucocorticoid on intrinsic glomerular antioxidant enzyme (AOE) activities. Munich-Wistar rats were treated with daily i.p. injection of vehicle or methylprednisolone [MP, 15 mg/kg body wt, (MP15)] either for three days or nine days. Glomeruli isolated from rats given MP15 had significantly higher activities of total (T-) and manganese (Mn-) superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase than vehicle-treated rats (P less than 0.05). MP15-treated rats were subjected to intrarenal arterial infusion of hydrogen peroxide (35 mumol over 1 hr). Values for urinary protein excretion rate (UprV) after hydrogen peroxide infusion were markedly lower in rats pretreated with MP15 for both three days and nine days than in untreated rats (109 +/- 18 and 55 +/- 24 vs. 416 +/- 73 micrograms/min, respectively, both P less than 0.005). To test whether the same therapeutic intervention attenuates reactive oxygen species (ROS)-mediated glomerular injury in another model, rats given a single i.v. dose of puromycin aminonucleoside (PAN) (50 mg/kg body wt) were treated with daily i.p. injection of vehicle or MP15. Two days after PAN administration, when compared to vehicle-treated controls, PAN rats given MP15 had significantly higher activities of Mn-SOD, GSH-Px and catalase. After eight days of PAN injection, T- and Mn-SOD activities were, likewise, significantly higher in MP15- than vehicle-treated PAN rats. PAN rats given MP15 also had substantially less proteinuria, compared to PAN rats given vehicle alone, UprV averaging 32.3 +/- 9.4 versus 159.0 +/- 13.8 mg/24 hr (P less than 0.05). Elevated glomerular malondialdehyde (MDA) level characteristic of PAN rats was absent in rats treated with MP15. Moreover, epithelial foot process fusion and cell vacuolization seen in vehicle-treated PAN rats were markedly attenuated in MP15-treated PAN rats. These data indicate that the mechanism for therapeutic effect of glucocorticoids on ROS-mediated renal injuries includes an enhancement of endogenous glomerular AOE activities, which attenuates lipid peroxidation of glomerular tissue.
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PMID:Glucocorticoid activates glomerular antioxidant enzymes and protects glomeruli from oxidant injuries. 194 78

The mechanism of cellular processes responsible for proteinuria induced by adriamycin (ADR) remains unclear. In this study, we examined whether oxygen radicals contribute to the development of proteinuria in ADR-induced nephrosis. The peak concentration of malondialdehyde (MDA) of kidney was found on 8th day after ADR treatment in rats. ADR-treated rats received either superoxide dismutase (SOD, scavenger of O2-, catalase (CAT, scavenger of . H2O2) or dimethyl sulfoxide (DMSO, scavenger of OH). The SOD, CAT or DMSO treated groups had a significant suppression of urinary protein excretion, serum and renal MDA compared to ADR control group. There were also less severe renal morphologic changes in the former three groups vs the ADR controls. These data provide indirect evidence that oxygen radicals generated by ADR are important mediators of ADR-induced proteinuria.
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PMID:Role of oxygen radicals in adriamycin-induced nephrosis. 211 39

The perfused isolated kidney is a partial ischemic system that is characterised by glomerular proteinuria and release of glomerular heparan sulfate. Metabolic changes associated with the levels of glutathione, xanthine oxidase and glyceraldehyde 3-dehydrogenase indicated that oxygen radical metabolites were being produced during the perfusion. We have demonstrated that a mixture of oxygen metabolite scavengers containing mannitol, superoxide dismutase and catalase included in the perfusion medium significantly reduced protein excretion. Similar results were obtained with the administration of allopurinol to the rat 24h prior to kidney removal and allopurinol in the perfusion medium. [35S]Heparan sulfate loss from the glomerulus was totally inhibited by the scavenger mixture. These results suggest that reactive oxygen metabolites may be involved in damage to renal capillaries, specifically to heparan sulfate proteoglycan, which leads to proteinuria as a result of partial ischemia produced during perfusion.
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PMID:The inhibitory action of oxygen radical scavengers on proteinuria and glomerular heparan sulphate loss in the isolated perfused kidney. 214 Dec 55

In an attempt to examine the role of reactive oxygen species on bivalent hapten immune complex glomerulonephritis, superoxide dismutase (SOD) concentration in renal tissue was studied by Electron Spin Resonance (ESR) and the protective effect of radical scavengers were evaluated. Injection of immune complex (IC) induced severe glomerulonephritis, characterized by neutrophil and/or monocyte infiltration in glomeruli in an association with proteinuria. SOD concentration in renal tissue decreased when neutrophil and/or monocytes infiltration and proteinuria developed, indicating a possible role of reactive oxygen species on renal injury. SOD, superoxide scavenger, and catalase (CAT), which destroy hydrogen peroxide, apparently reduced proteinuria on 14th day (18.5 +/- 3.17 mg/day, 20.7 +/- 7.35 mg/day, respectively, in comparison with control group, 29.5 +/- 4.21 mg/day), but there was no statistical significance. On the other hand, hydroxy radical scavenger, dimethylthiourea (DMTU) significantly reduced proteinuria (15.3 +/- 4.21 mg/day) and remarkable improvement in renal histology was observed. It is concluded that reactive oxygen species, especially hydroxy radical, play a significant role on renal injury in bivalent hapten immune complex glomerulonephritis.
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PMID:[Role of reactive oxygen species (Ros) in model immune complex nephritis]. 214 98


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