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)

A single intravenous injection of adriamycin (ADR) results in marked proteinuria and glomerular morphological changes that are similar to minimal-change disease in humans. We examined the effect of superoxide dismutase (SOD) on ADR-induced proteinuria. ADR in a dose of 7.5 mg/kg body weight significantly increased urinary protein by day 14; proteinuria rapidly increased thereafter. Concurrent administration of SOD (50 mg/kg) over 30 min prior to and 30 min following ADR injection markedly reduced proteinuria. Twenty-one days after the treatment with SOD, the amount of urinary protein was 108.6 +/- 43.1 mg/24 h in the experimental animals, while it was 221.6 +/- 102.9 mg/24 h in the ADR control group (p less than 0.05). There were also less severe glomerular morphologic changes in the SOD group versus ADR controls. The protective effects of SOD provide indirect evidence that oxygen free radicals are important mediators of ADR-induced proteinuria.
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PMID:Suppressive effect of superoxide dismutase on adriamycin nephropathy. 155 5

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

The complement system is composed by 26 plasmatic proteins. The activation of either the classical or alternative complement pathway leads to the formation of the membrane attack complex C5b-C9 (MAC) which is capable of producing damage of the cellular membrane. MAC has been identified in renal biopsies from human and experimental, immune and nonimmune renal diseases, but it has not been possible to demonstrate any enzymatic activity on the glomerular basement membrane components (GBM). MAC can produce a lytic or a nonlytic effect on renal cells depending upon the dose used. The lytic effect in vitro has been demonstrated in epithelial, mesangial and endothelial cells, whereas the lytic effect in vivo has been described in a model of acute glomerulonephritis produced by the administration of monoclonal antibody anti-Thy 1.1. which reacts with mesangial cells. The nonlytic effect of MAC on renal cells is characterized by alterations in cell metabolism which can lead the production of prostaglandins, type IV collagen, reactive oxygen species, and a growth factor resembling interleukin I which can contribute to glomerular damage, to the modification of the filtration barrier permeability and hemodynamic changes in experimental glomerulonephritis. The effector mechanisms by which the complement system participates in the pathogenesis of glomerulonephritis are different in the various experimental models of nephritis. In nephrotoxic nephritis the complement pathway participates at least in 3 different ways: a) complement-neutrophil mediated injury, b) MAC dependent mechanism and c) producing hemodynamic alterations. In acute serum sickness the complement system beyond C2 is not necessary for the development of proteinuria and glomerular inflammation, but the MAC assembly seems to be important for the formation of large deposits. In the chronic serum sickness model, the complement system participates in the early proteinuria as well as in the histological expression of the disease. In the heterologous phase of Heymann's nephritis, the proteinuria is complement dependent whereas in the autologous phase the damage depends upon cellular mediated immunity. In passive Heymann's nephritis the complement system and particularly MAC, has a central role for the histological lesion of the epithelial cell as well as in the proteinuria. In conclusion, the complement system can mediate renal damage by the following mechanism: a) Releasing chemotactic factors which result in neutrophil recruitment and neutrophil mediated glomerular damage.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Role of complement in experimental glomerulonephritis]. 180 1

It was examined the physical fitness of 165 male laborer with a special respect to their physical performance. The research covered other factors, as well such as the somatic and circulatory parameters, the maximal oxygen uptake estimated by Astrand, i.e. the aerobe metabolism, the activity and the fitness of the nervous system, the possible proteinuria following loading, the health condition of the examined persons and also certain other factors concerning their way of life. On the basis of the results, the authors established that with the major share of the examined labourers (nine percent of them) it was impossible to carry out the exercises because of contraindication, and in the case of 46 percent the exercises had to be interrupted because of occurring of certain symptoms and exhaustion. The physical performance was unfavourably affected by the fact that the relative majority of the examined persons are overweight, and the lungs function, especially the MVV-value does not reach the predicted level. Only 32 percent has the optimal body weight, while 20-26 percent is overweight. The MVV-value is under the predicted level in the case of 67-76 percent. The estimated relative aerobe capacity reached 84-86 percent of the predicted value with those whose physical performance is moderate. The authors evaluated the accomplished examinations individually as well and summarized them in records of examination. The records were distributed among the factory medical consultants who applied them effectively in the health provision of the examined persons.
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PMID:[Physiological characteristics of the health status of workers performing physical labor]. 185 38

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

A novel series of (3-pyridylmethyl)benzoquinone derivatives was molecular designed and synthesized for the dual purpose of inhibiting thromboxane A2 and leukotriene biosynthesis enzymes and scavenging active oxygen species (AOS). They were evaluated for inhibition of TXA2 synthase, inhibition of 5-lipoxygenase, and for their scavenging activity of AOS using the thiobarbituric acid method. 2,3,5-Trimethyl-6-(3-pyridylmethyl)-1,4-benzoquinone (24, CV-6504) was the most promising derivative since it showed efficient AOS scavenging activity (inhibition of lipid peroxidation in rat brain homogenates: IC50 = 1.8 x 10(-6) M) as well as potent, specific, and well-balanced inhibitory effects on both enzymes (inhibitory effect on TXA2 synthase in human blood, IC50 = 3.3 x 10(-7) M; inhibitory effect on 5-lipoxygenase in human blood, IC50 = 3.6 x 10(-7) M). In adriamycin-induced proteinuria in a rat model, compound 24 at 10 mg/kg per day (po) suppressed proteinuria by more than 50%. The proteinuria, however, could not be reduced by single administration of an inhibitor specific for thromboxane A2 synthase [(E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid (2, CV-4151)] or for 5-lipoxygenase [2-(12-hydroxy-5,10-dodecadiynyl)-3,5,6-trimethyl-1,4-benzoquinone (1, AA-861)]. The proteinuria was also not reduced by administration of an AOS scavenger, 2-O-octadecylascorbic acid (4, CV-3611). Triple function compounds such as compound 24 that specifically inhibit both enzymes as well as scavenge AOS possess a variety of pharmacologically beneficial effects.
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PMID:Dual inhibitors of thromboxane A2 synthase and 5-lipoxygenase with scavenging activity of active oxygen species. Synthesis of a novel series of (3-pyridylmethyl)benzoquinone derivatives. 199 26

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


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