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 effects of a daily administration of an anti-converting enzyme inhibitor. Captopril (CPT) (100 mg/kg/orally), on the development of functional and morphological alterations induced in rats by a single injection (7.5 mg/kg/iv) of Doxorubicin (DXR) (Adriamycin*), were investigated. Twenty-four-hour protein excretion, urine output, food intake, water intake, and body weight gain were measured weekly for 30 days. Transmission and scanning electron microscopy observations were performed on kidney samples after 30 days. Four groups were studied. Group 1 were control rats. Group 2 were rats injected with DXR. Group 3 were rats injected with DXR and treated with CPT for 30 days. Group 4 were rats injected with DXR and treated with CPT for 15 days (CPT treatment started 15 days after DXR injection). Group 1 did not show significant functional or morphological changes. Group 2 showed severe proteinuria, significant increase in urinary volume within 2 weeks, significant body weight reduction and diffuse morphological changes. These changes mainly consisted of podocyte swelling, severe foot process fusion, and presence of casts within tubular lumen. Group 3, with respect to group 2, showed a significant reduction of the 24 h protein excretion and urine output. This group displayed morphological changes similar to those observed in group 2, but with a focal distribution. Group 4 showed functional and morphological changes comparable with those of group 2. It is concluded that CPT partially inhibits the development of the functional and morphological damage induced by DXR in the rat kidney. However, CPT did not influence the natural development of nephropathy when treatment started 15 days after DXR injection.
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PMID:Effects of captopril on the development of rat doxorubicin nephropathy. 151 5

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

The status of negative charge on RBC and glomeruli and its relation to proteinuria of adriamycin nephrosis in rats were studied by electron computerized picture analysis. The results showed that the negative charge (NC) on glomeruli decreased significantly at 48 hrs and 14 days after ADR injection although there was no proteinuria simultaneously. There was a positive relation between the changes of NC on glomeruli and those on RBC (r = 0.77, p less than 0.01), and there was negative relation between either of them and proteinuria respectively (r = -0.5140, p less than 0.05; r = -0.5231, p less than 0.01). The focal fusions of foot processes occurred prior to the onset of proteinuria.
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PMID:[The status of negative charge of the RBC and glomeruli and its relation to proteinuria in adriamycin nephrosis in rats]. 216 Dec 75

Prostatic adenocarcinoma was diagnosed in an 11-year-old neutered cat. Clinical signs of the disease included hematuria and a mass in the caudal portion of the abdomen. Prostatectomy was performed. Doxorubicin was administered IV at a dosage of 30 mg/m2 of body surface, followed by cyclophosphamide (300 mg/m2, IV). After 4 treatments, low urine specific gravity and proteinuria developed, and treatment was discontinued. The cat was euthanatized 10 months after surgery because of recurrence of the neoplasm. Necropsy revealed metastasis to the lungs and pancreas.
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PMID:Prostatic adenocarcinoma in a cat. 227 82

Rats receiving a single injection of either aminonucleoside of puromycin (PAN, 10 mg/100 g) or Adriamycin (ADR, 7.5 mg/kg) develop heavy proteinuria and tubulointerstitial nephritis. Interstitial mononuclear cells were markedly more intense in PAN- than in ADR-treated rats. The composition of cell infiltrates was characterised in frozen kidney sections using an immunoperoxidase staining method and a panel of specific monoclonal antibodies. The severe mixed cellular lesions observed in the PAN model on day 14 were dominated by ED1+ macrophages, OX6+ Ia-interstitial and OX8+ T-cytotoxic/suppressor cell surface markers. A similar but more discrete ADR-interstitial cell accumulation was observed on day 11 of the experiment. A correlation existed in the PAN model between the severity of interstitial nephritis and the degree of proteinuria. In contrast, there was no such correlation in ADR nephrosis. Administration of PAF antagonist (BN 52021), started on the first day and continued throughout the 4 weeks of the experiment, induced in both ADR and PAN-treated rats a partial reduction in the number of interstitial cell infiltrates. Glomeruli from normal control rats incubated with 3H acetate, substrate for lyso-PAF: acetyl-CoA acetyltransferase and ADR stimulated PAF generation. Although the precise mechanism of interstitial cell accumulation in these two models of nephrosis are still unknown, our results suggest that PAF could be an important factor involved in interstitial cell recruitment.
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PMID:Interstitial mononuclear cell infiltrates in experimental nephrosis: effect of PAF antagonist. 251 24

Cardiotoxicity of doxorubicin, 2 mg/kg i.p. twice weekly in rats, was assessed by serial electrocardiography and electron microscopy. The toxic effects were markedly inhibited by ICRF-159, 50 mg/kg p.o. given 1 h before doxorubicin. The development of nephropathy characterized by proteinuria, hyperlipidemia and glomerular and tubular changes was significantly retarded, and the degenerative changes of peripheral nerves were markedly reduced. On the other hand, ICRF-159 enhanced the depressant effects of doxorubicin on bone marrow function. Doxorubicin reduced body weight gain, caused ascites, decrease in heart and thymus weight, and increase in liver and kidney weight. These changes were also inhibited or attenuated by ICRF-159 pretreatment.
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PMID:Inhibition of cardiotoxic, nephrotoxic and neurotoxic effects of doxorubicin by ICRF-159. 684 96

Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular lesions in rats, resulting in persistent proteinuria and glomerulosclerosis. We studied the effects of dietary protein and of an angiotensin I converting enzyme inhibitor on the progression of this nephropathy and the evolution of the histological lesions, as well as mesangial macromolecule flow. Adriamycin nephropathy was induced by injecting a single iv dose of adriamycin (3 mg/kg body weight) into the tail vein of male Wistar rats (weight, 180-200 g). In Experiment I animals with adriamycin-induced nephropathy were fed diets containing 6% (Low-Protein Diet Group = LPDG), 20% (Normal-Protein Diet Group = NPDG) and 40% (High-Protein Diet Group = HPDG) protein and were observed for 30 weeks. In Experiment II the rats with adriamycin nephropathy were divided into 2 groups: ADR, that received adriamycin alone, and ADR-ENA, that received adriamycin plus enalapril, an angiotensin I converting enzyme inhibitor. The animals were sacrificed after a 24-week observation period. Six hours before sacrifice the animals were injected with 131I-ferritin and the amount of 131I-ferritin in the glomeruli was measured. In Experiment III, renal histology was performed 4, 8 and 16 weeks after adriamycin injection. At the end of Experiment I the tubulointerstitial lesion index was 2 for LPDG, 8 for NPDG, and 7.5 for HPDG (P < 0.05); the frequency of glomerulosclerosis was 19 +/- 6.1% in LPDG, 42.6 +/- 6% in NPDG, and 54 +/- 9% in HPDG (P < 0.05); and proteinuria was 61.1 +/- 25 mg/24 h in LPDG, 218.7 +/- 27.5 mg/24 h in NPDG, and 324.5 +/- 64.8 mg/24 h in HPDG (P < 0.05). In Experiment II, at sacrifice, 24-h proteinuria was 189 +/- 16.1 mg in ADR, and 216 +/- 26.1 mg in ADR-ENA (P > 0.05); the tubulointerstitial lesion index was 5 for ADR, and 5 for ADR-ENA (P > 0.05); the frequency of glomerulosclerosis was 40 +/- 5.2% in ADR and 44 +/- 6% in ADR-ENA (P > 0.05); the amount of 131I-ferritin in the mesangium was 214.26 +/- 22.71 cpm/mg protein in ADR and 253.77 +/- 69.72 cpm/mg protein in ADR-ENA (P > 0.05). In Experiment III, sequential histological analysis revealed an acute tubulointerstitial cellular infiltrate at week 4, which was decreased at week 8. Tubular casts and dilatation were first seen at week 8 and increased at week 16 when few glomerular lesions were found.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of dietary protein, angiotensin I converting enzyme inhibition and mesangial overload on the progression of adriamycin-induced nephropathy. 758 Oct 27

This paper reports the ameliorative effect of Probucol (Pb) on ADR-induced nephrotic rats. Male Wistar rats underwent unilateral nephrectomy followed by one-week subsequent intravenous injection of 4.0 mg/kg of ADR. The rats were then divided into 3 groups: Pb-treated, non-treated and the control. The control group received 0.9% saline (vehicle) by injection. The 24-hr urinary protein excretion was measured for 24 weeks. When the animals were sacrificed at weeks 4, 12, and 24, respectively, blood samples were collected for biochemical study and the kidneys were extracted for measurement of malondialdehyde (MDA). In the morphological study, glomerular volume, glomerular sclerosis in dex (GSI), and tubulointerstitial index (TII) were calculated. Pb treatment lowered the serum lipid level and 24-hr urinary protein excretion. Total cholesterol was closely correlated with the urinary protein. However, there was no difference in terms of glomerular volume, kidney weight and GSI between the two groups. Pb treatment suppressed the kidney tissue MDA and TII significantly, the values of which were mutually correlated. The 24-hr protein excretion was significantly correlated with TII, but not with GSI. The decreased proteinuria was explained on the basis of suppression of enhancement of intraglomerular pressure induced by interstitial lesion. The findings suggest that renoprotection of Pb may derive from the amelioration of interstitial lesions.
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PMID:[The ameliorative effect of probucol on adriamycin (ADR) induced nephrotic rats]. 773 Nov 4

The relation between plasma lipoprotein composition and renal apolipoprotein deposition was studied in nephrotic rats in which stable renal function had been monitored for 7 months after a single low dose of adriamycin (ADR, 3 mg/kg). Proteinuria was observed 3 weeks after ADR and increased progressively up to about 0.5 g/day (versus 0.07 g/day in controls; P < 0.001), while the creatinine clearance remained stable at about 80% of control values. Hypercholesterolaemia was observed 6 weeks after ADR, and increased progressively up to 7.0 +/- 1.0 mmol/l (versus 2.3 +/- 0.1 mmol/l in controls; P < 0.001). Cholesterol was primarily located in LDL2 and HDL2 lipoproteins. Plasma apolipoprotein (apo) A-I increased by more than 400% in the nephrotic rats (P < 0.001). Apo B and apo E increased by about 60% (P < 0.01), whereas apo A-IV remained unchanged. Focal sclerotic lesions in glomeruli had an incidence of 50 +/- 10% in ADR rats versus 2 +/- 1% in controls (P < 0.001). Immunohistochemistry revealed apo A-I and apo A-IV in the visceral epithelium. Apo E immunoreactivity and lipid deposits were observed in focal glomerular sclerotic lesions of ADR rats. Neither apolipoproteins nor lipids were detected in glomeruli of controls. Proximal tubular localization of apolipoproteins was extensive for apo A-I, apo A-IV and apo E, but no differences were observed in tubular deposition of apolipoproteins between ADR and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma lipoproteins and renal apolipoproteins in rats with chronic adriamycin nephrosis. 825 16

Recent studies have suggested that the progression of experimental chronic renal disease may be prevented by early use of antihypertensive drugs. It is unclear, however, whether such therapies may also affect established and progressive renal disease. In the present study we compared the effects of captopril (CEI) and diltiazem (CCB), started either at week 10 or at week 24 on the evolution of adriamycin nephropathy (AN). Rats were studied at weeks 7, 16, 24, 32, and 38 of the disease. None of the treatments influenced the development of nephrotic range proteinuria. The use of CCB from week 10 was even associated with increased proteinuria. The moderate hypertension of ADR rats was reduced to the same degree with both drugs. Inulin clearance (GFR) was significantly reduced in all ADR rats. However, in ADR rats treated with CEI from week 10 and in those treated with CCB from week 24, the GFR was relatively higher. Glomerular injury, evaluated by semiquantitative methods, was not ameliorated by CEI treatment. Earlier CCB treatment (week 10) worsened glomerular lesions, whilst CCB treatment initiated at week 24 reduced significantly the degree of mesangial expansion and focal glomerular sclerosis. We conclude that, in addition to their common antihypertensive action, the specific effect of drug therapy seems to be crucially time dependent.
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PMID:Effect of timing of antihypertensive therapy on glomerular injury: comparison between captopril and diltiazem. 839 29


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