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)

Results from several radical scavenger studies indirectly suggested an involvement of reactive oxygen species in the pathogenesis of puromycin aminonucleoside glomerulopathy. In this study, generation of reactive oxygen species was examined directly in glomeruli isolated from rats in the acute phase of puromycin aminonucleoside nephrosis and related to the changes in the glomerular antioxidant defense. Five and nine days after puromycin aminonucleoside injection, gross proteinuria, reduced creatinine clearances, and typical changes of glomerular morphology were present. Levels of reactive oxygen species were increased eightfold in glomeruli isolated 15 min after puromycin aminonucleoside injection, returned to baseline levels on days 1 and 5 after injection, and rose again to 14-fold on day 9 after injection, as determined by chemiluminescence with luminol. Further analysis of increased glomerular radical generation, using the chemiluminescence enhancer lucigenin and different radical scavengers, suggested a predominant involvement of hydroxyl radical and hydrogen peroxide in the initial increase in reactive oxygen species 15 min after puromycin aminonucleoside. Nine days after induction of nephrosis, primarily superoxide anion and hydroxyl radical were found to contribute to increased reactive oxygen species. Despite oxidative stress, antioxidant enzymes were not induced in the course of nephrosis. On the contrary, catalase and glutathione peroxidase activities declined 9 d after puromycin aminonucleoside injection. The results indicate that a transient increase in glomerular reactive oxygen species is sufficient to induce the oxidative glomerular injury observed in this model and that the glomerulus may not necessarily respond to oxidative stress with an induction of antioxidant enzymes.
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PMID:Reactive oxygen species and antioxidant defense in puromycin aminonucleoside glomerulopathy. 935 75

Growth and injury represent recurrent and related themes in the study of progressive renal disease. We have previously demonstrated that a prooxidant diet, one deficient in antioxidants, selenium and vitamin E, induces renal enlargement, proteinuria, mild tubulointerstitial disease and diminished glomerular filtration rate (GFR). Our present study represents continued examination of these processes. We demonstrate that these diets increase thymidine incorporation into DNA and net DNA content in renal tissue, and induce expression of the mRNA for the proto-oncogene, c-myc, and the histone, H2b. We localize increased DNA synthesis as occurring mainly in the distal renal tubular epithelium. These deficient kidneys also exhibit interstitial expansion that parallels the pattern of DNA synthesis in that both processes are more prominent in the medulla than in the cortex. mRNAs for collagens I, III and IV in conjunction with transforming growth factor-beta1 (TGF-beta1) are up-regulated in the kidney in rats maintained on the deficient diet. In complementary in vitro studies, the exposure of rat kidney fibroblasts, NRK 49F cells, to noncytolytic doses of hydrogen peroxide, induces collagen III, collagen IV and TGF-beta1 mRNA. Induction of these genes is also observed in mesangial cells so exposed to noncytolytic doses of hydrogen peroxide. A final aspect of our study was the examination of renal generation of hydrogen peroxide and the profile of the hydrogen peroxide-degrading enzymes. Deficient kidneys exhibit increased mitochondrial generation of hydrogen peroxide independent of oxygen consumption but in conjunction with suppression of glutathione peroxidase mRNA and activity. Lipid peroxidation was increased twofold in the cortex and medulla of the deficient kidneys. Surprisingly, catalase activity, measured in the cortex and medulla, and whole kidney catalase mRNA were also reduced in rats maintained on the antioxidant deficient diet, effects that may further compromise the clearance of hydrogen peroxide. These changes in catalase represent an adverse response to this dietary deficiency, and may be relevant to decreased catalase activity described in chronic renal insufficiency. Thus, a chronic prooxidant state, with features that mimic those of clinical uremia, increases DNA synthesis of renal tubular epithelium, induces mRNA expression for collagens I, III and IV in conjunction with the mRNA for the fibrogenic cytokine, TGF-beta1. Oxidants also induce collagen III, collagen IV and TGF-beta1 mRNA in vitro.
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PMID:Redox regulation of renal DNA synthesis, transforming growth factor-beta1 and collagen gene expression. 946 Oct 96

In rats with five-sixths nephrectomy (remnant kidney), blood pressure, glomerulosclerosis, and proteinuria are significantly reduced by administration of the angiotensin-converting enzyme inhibitor enalapril, during 16 weeks after reduction of the nephron number. The activity of catalase in remnant-kidney cortex homogenate is not influenced by enalapril treatment; the activities of superoxide dismutase and glutathione peroxidase are significantly increased. Elevated lipid peroxidation in cortex homogenates, evaluated by malondialdehyde and 4-hydroxynonenal concentrations, is not changed by treatment. Supplementation of dietary vitamin E to enalapril treatment does not alter antioxidant enzyme activities when compared to enalapril monotherapy. These results show that enalapril improves the balance between reactive oxygen intermediates and antioxidant enzymes in the remnant-kidney cortex of the rat. This finding may in part explain the protective effect of angiotensin-converting enzyme inhibitors on the progression of glomerulosclerosis.
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PMID:Enalapril increases antioxidant enzyme activity in renal cortical tissue of five-sixths-nephrectomized rats. 1052 41

Eighteen children with steroid-sensitive nephrotic syndrome (SSNS) were studied. The control group comprised 20 healthy children. The following indirect parameters of reactive oxygen species activity were determined in nephrotic patients during four stages of the disease (full relapse before prednisone administration, disappearance of proteinuria, prednisone cessation, unmaintained remission): plasma malondialdehyde (MDA) levels, copper/zinc superoxide dismutase (CuZn SOD) activity and glutathione peroxidase (GPX) activity in erythrocytes, reduced glutathione (GSH) and vitamin C levels in whole blood, and vitamin E level in serum. Increased MDA levels, reduced vitamin C levels, and enhanced CuZn SOD activity were found in relapse. GSH concentration was high during all four stages. Vitamin E level was also increased, parallel to the pattern of serum lipids. GPX activity remained low during the proteinuria stage and in remission. We conclude that the majority of abnormal findings can be attributed to the hyperlipidemia of NS. Low GPX activity may be a factor limiting the antioxidant capacity in NS. The present study is inconclusive regarding the role of free radicals in the proteinuria of NS.
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PMID:Antioxidant status of children with steroid-sensitive nephrotic syndrome. 987 20

We have investigated the influence of a novel angiotensin II type 1 receptor antagonist, candesartan cilexetil, on the oxidative state of renal tissue and renal function in 5/6 nephrectomized rats, and compared its effects with those of an angiotensin-converting enzyme inhibitor, enalapril. Candesartan cilexetil (1 and 5 mg/kg per day), enalapril (5 mg/kg per day) and vehicle were orally administered once daily for 16 weeks after 5/6 nephrectomy. There was a marked degree of proteinuria evident prior to treatment, an average of 5.69 mg/mg creatinine in the nephrectomized rats, vs 1 to 2 mg/mg creatinine in the control group matched for species and body weight. Inhibition of development of proteinuria by candesartan cilexetil was dose dependent. Enalapril also significantly blunted the rise in urinary protein. Malondi-aldehyde content in the homogenate from the renal cortex increased significantly in the nephrectomized rats compared to control animals. This elevation of malondi-aldehyde content was unaffected by administration of either candesartan cilexetil or enalapril. Antioxidative enzyme (glutathione peroxidase, superoxide dismutase, and catalase) activities in the renal tissue were not affected by any active treatment. Elevation of lipid peroxide in remnant renal tissue suggests that oxidative stress may contribute to the progression of renal injury in the nephrectomized rats. Neither candesartan cilexetil nor enalapril affected antioxidant defenses in renal tissue in nephrectomized rats, indicating that mechanisms other than alteration in oxidative stress are involved in the renoprotective effects of candesartan cilexetil and enalapril.
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PMID:Effects of candesartan cilexetil on oxidative state and renal function in 5/6 nephrectomized rats. 1007 23

The present study investigated the effect of curcumin on adriamycin (ADR) nephrosis in rats. The results indicate that ADR-induced kidney injury was remarkably prevented by treatment with curcumin. Treatment with curcumin markedly protected against ADR-induced proteinuria, albuminuria, hypoalbuminaemia and hyperlipidaemia. Similarly, curcumin inhibited ADR-induced increase in urinary excretion of N-acetyl-beta-D-glucosaminidase (a marker of renal tubular injury), fibronectin and glycosaminoglycan and plasma cholesterol. Curcumin restored renal function in ADR rats, as judged by the increase in GFR. The data also demonstrated that curcumin protected against ADR-induced renal injury by suppressing oxidative stress and increasing kidney glutathione content and glutathione peroxidase activity. In like manner, curcumin abolished ADR-stimulated kidney microsomal and mitochondrial lipid peroxidation. These data suggest that administration of curcumin is a promising approach in the treatment of nephrosis caused by ADR.
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PMID:Curcumin prevents adriamycin nephrotoxicity in rats. 1069 26

1. We have evaluated the effects of the angiotensin-converting enzyme inhibitor enalapril on renal function and oxidative status in the kidney of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneous onset of type 2 diabetes mellitus. 2. Enalapril (5 mg/kg) or vehicle (distilled water) was given once daily by gavage to 22-week-old male OLETF rats for 32 weeks. Long-Evans Tokushima Otsuka (LETO) rats, the control animals for OLETF rats, received vehicle alone (n = 10 in each group). 3. Enalapril attenuated the rise in blood pressure mildly, but significantly. Enalapril significantly blunted the development of proteinuria without a significant effect on creatinine clearance. At the end of the study period, the lipid peroxide content in the renal cortex was significantly increased in OLETF compared with LETO rats, in which enalapril had no effect on lipid peroxide content. Enalapril enhanced the activity of catalase in the renal cortex of OLETF rats, but had no effect on the activity of either superoxide dismutase or glutathione peroxidase. 4. These results suggest that oxidative stress may be involved in the development of nephropathy in type 2 diabetes. Enalapril exhibited renoprotective effects without changing lipid peroxides in the kidney, suggesting that the beneficial effects of the compound on diabetic renal damage in OLETF rats may not be mediated through an anti-oxidative action.
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PMID:Effect of enalapril on diabetic nephropathy in OLETF rats: the role of an anti-oxidative action in its protective properties. 1155 23

Recently, numerous studies have shown antioxidant actions of melatonin. Melatonin at both physiological and pharmacological levels stimulates glutathione peroxidase, glutathione reductase and superoxide dismutase activities in the brains of rats and chickens. This study was designed to evaluate the effect of melatonin on nephropathy and oxidative stress under constant light exposure. Nephropathy was induced by adriamycin administered in a single dose (25 mg kg(-1) b.w., i.p.). Melatonin was injected i.p. (1,000 microg kg(-1) b.w./day). Malondialdehyde, reduced glutathione, glutathione peroxidase, glutathione reductase, glutathione transferase, catalase and superoxide dismutase were determined in kidney. Urea, creatinine and total proteins in plasma and proteinuria were evaluated and melatonin was determined. Results show a decrease in melatonin levels. Similar effects occurred with the antioxidant enzyme activities and reduced glutathione. Likewise, adriamycin and constant light induced significant enhancement of malondialdehyde. All changes induced both by adriamycin and constant light were reverted to normal by melatonin administration. Constant light exposure was associated with an increase in oxidative stress and nephropathy induced by adriamycin. Treatment with melatonin decreased lipid peroxides, and permitted a recovery of reduced glutathione, scavenger enzyme activity and parameters of renal function.
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PMID:Melatonin effect on renal oxidative stress under constant light exposure. 1257 19

Proteinuria is an independent risk factor for progression of renal diseases. Glia maturation factor-beta (GMF-beta), a 17-kDa brain-specific protein originally purified as a neurotrophic factor from brain, was induced in renal proximal tubular (PT) cells by proteinuria. To examine the role of GMF-beta in PT cells, we constructed PT cell lines continuously expressing GMF-beta. The PT cells overexpressing GMF-beta acquired susceptibility to cell death upon stimulation with tumor necrosis factor-alpha and angiotensin II, both of which are reported to cause oxidative stress. GMF-beta overexpression also promoted oxidative insults by H2O2, leading to the reorganization of F-actin as well as apoptosis in non-brain cells (not only PT cells, but also NIH 3T3 cells). The measurement of intracellular reactive oxygen species in the GMF-beta-overexpressing cells showed a sustained increase in H2O2 in response to tumor necrosis factor-alpha, angiotensin II, and H2O2 stimuli. The sustained increase in H2O2 was caused by an increase in the activity of the H2O2-producing enzyme copper/zinc-superoxide dismutase, a decrease in the activities of the H2O2-reducing enzymes catalase and glutathione peroxidase, and a depletion of the content of the cellular glutathione peroxidase substrate GSH. The p38 pathway was significantly involved in the sustained oxidative stress to the cells. Taken together, the alteration of the antioxidant enzyme activities, in particular the peroxide-scavenging deficit, underlies the susceptibility to cell death in GMF-beta-overexpressing cells. In conclusion, we suggest that the proteinuria induction of GMF-beta in renal PT cells may play a critical role in the progression of renal diseases by enhancing oxidative injuries.
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PMID:Induction of glia maturation factor-beta in proximal tubular cells leads to vulnerability to oxidative injury through the p38 pathway and changes in antioxidant enzyme activities. 1279 1

Abnormal glomerular glycosaminoglycan metabolism is involved in the onset of the morphological and functional aberrations of glomerulopathies. In the present study, a heparin derivative, low-molecular-weight heparin, was tested for its ability to afford renoprotection in an established model of experimental glomerulopathy. Two groups of male albino rats of the Wistar strain (140 +/- 10 g) received a single intravenous injection of adriamycin (7.5 mg/kg) to induce glomerulopathy, and one of them received low-molecular-weight heparin (Certoparin Sodium, Troparin; 300 microg/day/rat s.c.) treatment, commencing on day 8, for a week. Urinary protein/creatinine ratio, serum albumin, urea, uric acid and creatinine clearance were evaluated. Renal cell injury was assessed in terms of renal tissue lactate dehydrogenase, aminotransferases (aspartate and alanine transaminases) and alkaline phosphatase activities, as well as renal antioxidant status (superoxide dismutase, catalase and glutathione peroxidase, reduced glutathione, vitamins E and C). The kidney tissue was subjected to histopathologic examination. Low-molecular-weight heparin significantly reduced proteinuria and improved creatinine clearance and serum albumin levels in the rats with glomerulopathy. The significant rise in serum uric acid in the rats with glomerulopathy was reversed by low-molecular-weight heparin. Altered tissue enzyme activities in response to injury, oxidative stress challenged renal antioxidant system and abnormal renal histology were observed in the untreated nephrotic rats, while low-molecular-weight heparin treatment protected the nephrotic rats against these changes. Thus, in this study, low-molecular-weight heparin was evaluated for its role in combating glomerular injury, on the basis of some salient biochemical parameters, oxidative injury indices and histologic picture. The ability of low-molecular-weight heparin to restore glomerular anatamo-functional features in this nephrotoxic condition illuminates its multi-faceted renoprotective role.
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PMID:The cytoprotective role of a low-molecular-weight heparin fragment studied in an experimental model of glomerulotoxicity. 1457 5


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