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)

This study focused on the utility of interferon gamma (IFN gamma) as an anti-fibrotic drug in renal experimental fibrosis; the nephropathy was induced by two doses of Adriamycin (ADR) in 20 Sprague Dawley rats, 10 of which were randomly assigned to receive IFN gamma (45,000 UI) on alternate day for 16 weeks. At the end of the follow up, ADR rats treated with IFN gamma developed massive proteinuria, slight renal insufficiency, and presented diffuse glomerulosclerosis, tubulo interstitial infiltration and fibrosis. No difference was found in the composition of tubulo-interstitial infiltrates, mainly consisting in CD4+T lymphocytes with a minor component of CD8+T cells, in comparison with rats treated with ADR alone. These observations demonstrate the inefficacy of a protracted high-dose treatment with IFN gamma in chronic experimental nephropathy with interstitial fibrosis.
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PMID:Protracted high-dose interferon gamma therapy for chronic experimental nephropathy. 828 79

1. Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular lesions in rats, resulting in persistent proteinuria and glomerulosclerosis. 2. The effect of urine volume on the progression of adriamycin-induced nephropathy was studied in 70 male Wistar rats (180-200 g) observed for 30 weeks and separated into 4 groups: healthy control group (HCG, N = 10) inoculated i.v. with 1 ml of saline, and nephrotic groups inoculated iv with a single dose of adriamycin of 3 mg/kg body weight. The nephrotic rats were separated into 3 groups (N = 20): nephrotic control group (NCG) receiving only adriamycin; dehydrated nephrotic group (DNG) water deprived for 36 h within each 48-h period, and furosemide nephrotic group (FNG) treated with 12 mg/dl furosemide, and 0.9 g/dl NaCl in the drinking water. 3. The 30-week survival rates of the DNG (100%) and HCG (100%) were significantly higher than those of the NCG (85%) and FNG (55%). 4. The proteinuria observed in the HCG (range, 7.38 +/- 0.7 to 13.6 +/- 1.27 mg/24 h) was significantly lower than that observed for all the nephrotic groups throughout the experiment. The DNG presented significantly less proteinuria (range, 42.71 +/- 6.83 to 140.10 +/- 19.22 mg/24 h) than the NCG (range, 35.32 +/- 7.64 to 250.00 +/- 25.91 mg/24 h) from week 10 on. There was no significant difference between the mean 24-h proteinuria of the NCG (range, 35.32 +/- 7.64 to 250.00 +/- 25.91 mg/24 h) and the FNG (range, 35.82 +/- 7.91 to 221.54 +/- 26.74). 5. The mean frequency of damaged glomeruli was 0.3% +/- 0.3 for HCG, 42% +/- 6% for CNG, 40.8% +/- 8% for DNG, and 47% +/- 14% for FNG. The median value of the tubulointerstitial lesion, evaluated by a semiquantitative method, was 0 in HCG, 10 in CNG, 8.5 in DNG and 9.5 in FNG (P < 0.05 for all groups compared to HCG). 6. The data indicate that reduction of urine volume has a protective effect on adriamycin-induced nephropathy.
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PMID:Reduction of urine volume ameliorates adriamycin-induced nephropathy. 829 29

Adriamycin (ADR) induces glomerular damage in rats with persistent severe proteinuria which reaches a peak 15 days after a single 5 mg/kg intravenous (i.v.) injection. We studied in ADR-treated rats the effects of a low-protein (6%) diet (LPD) supplemented with keto acids on urinary protein and glycosaminoglycan (GAG) excretion and glomerular GAG contents. Animals were divided into three groups: group 1 was used as control, and groups 2 and 3 received a single i.v. injection of ADR; group 2 was fed a standard diet (21% protein) and group 3 an LPD. After ADR, group 2 developed heavy proteinuria and showed a progressive increase in urinary GAG excretion starting a few days after the beginning of proteinuria onset and persisting throughout the experiment. After ADR, group 3 (LPD treatment) did not develop proteinuria, and the level of urinary GAGs was comparable to that of controls. The glomerular GAG level in ADR-treated rats was greatly reduced as compared to controls; this decrease was partly eliminated in rats on an LPD. These results suggest that an LPD has a direct effect on cellular GAG production and turnover in ADR-induced glomerulonephritis.
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PMID:Effects of a low-protein diet on urinary glycosaminoglycan excretion in adriamycin-treated rats. 832 58

In this study, we examined the progression of chronic Adriamycin (ADR) nephropathy in mild leukopenic rats and tried to define the possible relationship between tubulointerstitial lesions and proteinuria in this model. Chronic ADR nephropathy was induced by 2 doses of ADR (2 mg/kg) in 32 Sprague-Dawley rats. Eight of these were randomly assigned to cyclophosphamide treatment (50 mg/kg), given intravenously every week, to keep the blood leukocyte count constantly lower than 5,000/mm3. Serial parameters were followed for 16 weeks including clearance studies with iothalamate and p-aminohippurate and the analysis of urinary protein composition by: (a) an enzymatic assay for beta-glucosidase; (b) specific ELISA using antibodies against rat albumin and RBP, and finally (c) two-dimensional electrophoresis. ADR-treated rats rapidly (within 2 weeks) developed massive proteinuria which was in constant increment throughout the disease evolution in each single component (i.e., high and low molecular weight proteinuria, enzymuria) and developed renal insufficiency. At week 8, in ADR rats, glomerulosclerosis was mild whereas tubulointerstitial infiltrates predominated, characterized mainly by CD4+ T lymphocytes while CD8+ T lymphocytes were inconspicuous, and macrophages were only occasionally present. All such alterations had worsened after 16 weeks when the tubulointerstitial infiltration was associated with marked interstitial fibrosis and tubular atrophy. Leukopenia induced by cyclophosphamide was in all cases associated with a net amelioration of renal histopathology reducing tubulointerstitial infiltrates (by 40%) and glomerulosclerosis (33 +/- 5 vs. 52.2 +/- 7.5% sclerotic glomeruli) and also ameliorated glomerular filtration indexes (Cl 780 +/- 40 vs. 447 +/- 66 microliters/min/kg-1). In spite of these differences, albuminuria and urinary-retinol-binding protein were comparable at weeks 4, 8 and 16 in this group, while urinary beta-glucosidase was decreased at week 16 (p < 0.001) in cyclophosphamide-treated rats. No other qualitative changes in urinary proteins were detectable by 2-dimensional electrophoresis during the disease development. We concluded that chronic leukopenia prevents interstitial cellular infiltration by lymphocytes, interstitial fibrosis and slows down the decline of renal function typical of chronic ADR nephropathy. Glomerulosclerosis is also reduced in leukopenic rats without any appreciable changes in the urinary excretion of high molecular weight proteins deriving from the glomerulus. Finally, the improvement in tubulointerstitial alteration is associated with the reduction in urinary lysosomal enzymes. Tubulointerstitial alterations are implicated with a prominent role in the progression towards renal failure in chronic ADR glomerulopathy.
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PMID:Progression of chronic adriamycin nephropathy in leukopenic rats. 844 56

The effect of orally available, nonpeptide vasopressin V1 and V2 receptor antagonists on chronic progressive glomerular disease was investigated in Wistar rats with Adriamycin-induced nephropathy. At weeks 0 and 3, Adriamycin was injected twice, and at week 3 drugs started to be given as follows: groups 2 and 3 were treated with V1 and V2 antagonists, respectively, while the untreated group 1 served as control. To block the effects of vasopressin totally, both V1 and V2 antagonists were simultaneously administered (group 4). At weeks 8 and 10, V1 and V2 antagonists given either alone or combined significantly reduced the urinary protein excretion to the same levels. Urinary volume increased in groups 3 and 4 from week 4. Systolic blood pressure did not significantly increase in all groups during the study. Histological alterations in the kidney of groups 2, 3 and 4 were significantly attenuated compared to the control. These results suggest that both vasopressin V1 and V2 agonism plays a role in the pathophysiology of Adriamycin-induced nephropathy despite plasma levels of vasopressin within the normal range. These findings also lead to the notion that in some types of nephrotic patients these orally available V1 and/or V2 receptor antagonists may be effective for reduction of proteinuria and for retardation of progression of renal failure.
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PMID:Evidence for the involvement of vasopressin in the pathophysiology of adriamycin-induced nephropathy in rats. 873 Apr 39

To clarify the pathogenesis of focal-segmental glomerulosclerosis, we investigated the sex-related difference and the effect of castration in Adriamycin (ADR) induced nephropathy of Sprague-Dawley rats. At 5 weeks of age, group 1 female and group 2 male rats were sham operated, and group 3 male rats were castrated. ADR 2 mg/kg was intravenously administered to all rats at 8 weeks of age twice at a 20-day interval. Body weight, blood pressure, urinary protein, and serum constituents were investigated every 4 weeks, 4-20 weeks after the second ADR injection. Each group was studied morphologically 12 and 20 weeks after the second ADR injection. ADR induced massive proteinuria in male rats, whereas it induced significantly lower proteinuria in female rats, and castration significantly reduced proteinuria of male rats to an extent equal to the levels seen in female rats. Control male rats had significantly lower serum albumin levels and a significantly greater impairment of renal function (blood urea nitrogen and creatinine levels) than the female rats or the castrated male rats at 20 weeks. The glomerulosclerosis index was significantly higher in control male rats than in female rats, and castration attenuated glomerular injury of male rats to an extent close to the levels seen in female rats, though there was a significant difference in the glomerulosclerosis index between female rats and castrated male rats. The three groups did not differ in blood pressure and plasma somatomedin C and serum growth hormone levels, whereas the plasma testosterone levels were decreased to undetectable in female and castrated male rats, resulting in a reduction of sex-related low molecular weight protein in urine. These observations suggest that sex hormones such as testosterone and estrogen and/or sex-related low molecular weight protein regulated by testosterone and estrogen may play a contributory role in sex differences in the progression of glomerulosclerosis in ADR-treated rats.
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PMID:Sex difference in progression of adriamycin-induced nephropathy in rats. 895 69

Ciclosporin A (CsA) can reduce proteinuria in various forms of human and experimental glomerulopathies. This antiproteinuric effect can be the result of a decrease of immunological damage, a decrease in the glomerular filtration rate (GFR), or a change in the permselective properties of the glomerular capillary wall. In this study we investigated the effect of CsA on Adriamycin-induced nephropathy in rats. A single intravenous injection of Adriamycin (5 mg/kg body weight) induced a severe nephrotic syndrome with a massive albuminuria (+/- 400 mg/24 h from 3 weeks onwards) and a hypoalbuminemia (+/- 7 mg/ml after 5 weeks). The IgG/albumin selectivity index was 0.16 +/- 0.05, indicating a preferential loss of albumin. A 5-day treatment with CsA reduced the albumin excretion by almost 50% (from 336 +/- 91 to 178 +/- 58 mg/24 h; p = 0.002) and induced an increase in the serum albumin level (from 7.1 +/- 4.1 to 12.8 +/- 3.2 mg/ml; p = 0.002) in contrast to the vehicle olive oil (OO). CsA also decreased the GFR by 40% (from 0.74 +/- 0.11 to 0.41 +/- 0.11 mg/ml/100 g body weight; p = 0.002). Albuminuria corrected for the GFR (fractional excretion of albumin, FE(alb)) was still significantly lower in CsA-treated than in OO-treated animals (FE(alb) CsA: 1.35 +/- 0.88, FE(alb) OO: 3.17 +/- 2.29%; p = 0.0005). This suggests that other factors are also involved in the reduction of albuminuria. To exclude that CsA has an effect on the tubular reabsorption of albumin, we evaluated the blockade of the tubular reabsorption by lysine and found no difference in albuminuria between the CsA- and OO-treated groups. These experiments suggest that the antiproteinuric effect of CsA is not (only) due to a decrease in the GFR, but also to a decrease of the enhanced permeability of the glomerular capillary wall for albumin.
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PMID:Antiproteinuric effect of ciclosporin A in adriamycin nephropathy in rats. 906 57

The effect of melatonin (MEL) on the nephropathy and the oxidative stress induced by a single and high dose of Adriamycin (AD) has been studied in Wistar male rats. MEL (50 microg/kg/day) was injected intraperitoneally 3 and 7 days, respectively, before and after AD injection (20 mg/kg i.p.). Trunk blood was drawn and triglycerides, total cholesterol, phospholipids, high-density lipoprotein cholesterol, urea, creatinine, total protein, lipoperoxides, and reduced glutathione (GSH) levels and catalase activity (CAT) were determined in serum. In kidney homogenates, lipoperoxides, GSH, and CAT were measured as well as total protein in urine. AD administration resulted in hyperlipidemia and high-grade proteinuria and a marked increase in serum lipoperoxides, urea, and creatinine. In the kidney, the increase in lipoperoxides was accompanied by a significant decrease of GSH and CAT. The efficiency of MEL was specially remarkable in restoring GSH, CAT, and proteinuria to the levels of controls. These results confirm the involvement of free radicals in the pathogenesis of nephrotoxicity induced by AD. Likewise, they show the high antioxidative power of MEL and its marked effect on the prevention and suppression of this nephropathy.
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PMID:Hyperlipidemic nephropathy induced by adriamycin: effect of melatonin administration. 922 37

The interaction of cells within the glomerulus plays an important role in the development and progression of glomerular disease. To investigate the interaction of glomerular mesangial cells (GMC) and epithelial cells (GEC), and mediator(s) of this interaction, we investigated the effect of Adriamycin (doxorubicin hydrochloride)-induced (ADR) rat GMC-conditioned medium (GMC-CM) on the incorporation of 35S, 3H-leucine, and 3H-thymidine in normal rat GEC, as well as 3H-thymidine uptake by normal rat GMC in response to ADR-rat GEC-CM. In addition, changes in the responsiveness to interleukin-6 (IL-6) and the products of IL-6 were assessed in ADR-rat GMC. The results showed that: (1) GMC-CM of ADR-rat with heavy proteinuria stimulated GEC proliferation and the synthesis of sulfated compounds and protein, while the GEC-CM of ADR-rat from the same nephrotic period increased GMC proliferation; (2) the ADR-rat GMC had altered responsiveness to IL-6 and its products. The stimulation index results demonstrated the interaction of GMC and GEC in the ADR-induced rat model, and that this interaction related closely to the degree of proteinuria and was mediated by soluble products of the damaged glomerular cell.
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PMID:The interaction of glomerular mesangial cells and epithelial cells. 963 36

Hyperlipidemia associated with nephrotic syndrome may play a role in the deterioration of renal function. Tsutsumi et al have previously reported that the novel compound NO-1886 increases lipoprotein lipase (LPL) activity, resulting in a reduction of plasma triglycerides and an elevation of high-density lipoprotein (HDL) cholesterol in normal rats. The aim of this study was to ascertain whether NO-1886 suppresses the renal injury by treatment of the hyperlipidemia in an Adriamycin (Kyowa Hakko Kogyo, Tokyo, Japan) induced nephrosis rat model fed a high-protein diet that induced renal dysfunction and tubulointerstitial injury. Administration of Adriamycin caused hyperlipidemia, proteinuria, and edema with ascites in rats in 4 weeks. Furthermore, a combination of Adriamycin and a high-protein diet increased plasma creatinine and blood urea nitrogen (BUN) and decreased plasma albumin. Histologically, in Adriamycin-treated rats, marked interstitial cellular infiltration, tubular lumen dilation, and tubular cast formation in the kidney were observed. NO-1886 decreased plasma triglyceride and increased HDL cholesterol in Adriamycin-induced nephrotic rats. NO-1886 treatment reduced plasma creatinine and BUN levels and increased plasma albumin in Adriamycin-treated rats; it also ameliorated the ascites and proteinuria. Histologically, NO-1886-treated rats showed a quantitatively significant preservation of tubulointerstitial lesions. These data suggest that NO-1886 may have a protective effect against Adriamycin-induced nephrosis with tubulointerstitial nephritis in rats by a modification of the plasma lipid disorder.
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PMID:Effect of the lipoprotein lipase activator NO-1886 on adriamycin-induced nephrotic syndrome in rats. 1083 Nov 67


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