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)

TI-31 (TEI-3096; 6-p-chlorobenzyl-5H-2,3,6,7-tetrahydro-5,7-dioxothiazolo[3,2-a]pyr imidine) is a novel immunomodulator. Various nephritic changes observed in female NZB/NZW F1 (B/W) mice with aging were suppressed by TI-31 when administered orally 5 times per week for 16 weeks at doses of 2, 10, or 50 mg/kg. It suppressed proteinuria, oliguria, the decrease of erythrocyte count, and increase of serum urea nitrogen, immune complex and anti-double-stranded DNA antibody levels. The anti-nephritic effect of TI-31 was confirmed by histopathological evaluation. TI-31 (10 mg/kg) could improve both the elevated polyclonal B cell activation and the depressed antibody response to sheep red blood cells in B/W mice, in comparison with age- and sex-matched BALB/c mice, without any effect on the antibody response in these normal mice. These findings indicate that TI-31 may inhibit B/W nephritis by regulating the antibody production through a mechanism different from that of anti-inflammatory drugs or immunosuppressants.
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PMID:Inhibitory effect of TI-31 on autoimmune nephritis in NZB/NZW F1 mice through regulation of the immune response. 349 22

The progression of adriamycin-induced nephrotic syndrome in rats was studied over a 3-month period. The effect of an angiotensin-converting enzyme inhibitor, captopril, on this model of renal disease, was also studied. Two weeks following a single iv injection of adriamycin, rats were divided into two treatment groups: one received a daily po dose of captopril and the other received a placebo. Measurements of renal function were performed at 4, 8, and 11 weeks following the initiation of therapy. Necropsies and light microscopic evaluation of the kidneys were performed at the end of the treatment period. Functional and morphologic alterations in both groups of rats were compared to each other and to normal age/weight-matched control rats studied over the same time period. At 13 weeks following the administration of adriamycin, both treatment groups had significant renal dysfunction when compared to normal controls. In addition to severe proteinuria, rats receiving adriamycin exhibited polyuria, polydipsia, increased plasma urea nitrogen and plasma creatinine, and decreased endogenous creatinine clearance. They had severe generalized kidney lesions characterized by tubular dilation and atrophy, cast formation, interstitial fibrosis and lymphocytic infiltration, and focal, global glomerulosclerosis. The histopathologic ranking of the kidneys was correlated with some antemortem laboratory parameters but not with the degree of proteinuria. Captopril had no ameliorating effects on the progression of renal disease. Certain findings indicate that captopril may actually have promoted the deterioration of renal function. We conclude that adriamycin-induced nephrotic syndrome in the rat is a progressive disease resulting in generalized renal dysfunction, and that captopril, at the dose given in this experiment, is unable to slow the progression of the disease.
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PMID:The progression of adriamycin-induced nephrotic syndrome in rats and the effect of captopril. 351 65

Nephrotoxic effect of ionic and non-ionic contrast media was examined in a doubleblind study by evaluation of serum creatinine, blood urea nitrogen, urine volume, urinary protein excretion and erythrocyturia before and after selective renovasography. In 19 of 22 patients reliable results were obtained. With optimal hydration before and after renovasography no significant differences between both administered contrast media (Rayvist 300 and Omnipaque 300) could be found by evaluation of the aforementioned parameters. In 3 patients with preexistent proteinuria (greater than 200 mg/l) urine protein excretion remained at the same or a lower level after application of the non-ionic contrast medium Omnipaque 300. Three patients with proteinuria tended to increase the proteinuria after administration of the ionic contrast medium (Rayvist 300) up to 48 h after angiography indicating a higher nephrotoxic potential of ionic contrast media in patients with preexistent renal disease. The constant values of urine volume and serum creatinine indicate an absence of clinically relevant nephrotoxicity of both contrast media in this study when administered in well-hydrated patients. This emphasizes the importance of sufficient hydration in prophylaxis of nephrotoxic effects, especially in patients with risk factors.
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PMID:[Nephrotoxicity of ionic and nonionic contrast media in selective renovasography]. 352 Oct 47

Correlation between the deposition of alpha 2-plasmin inhibitor (alpha 2-PI), which is one of the inhibitory factors of fibrinolytic activities, in the glomeruli and the effects of urokinase therapy in patients with IgA nephropathy is described. Urokinase (UK) is a plasminogen activator derived from fresh human urine. Urinalysis and measurements of renal function tests, i.e., serum creatinine, blood urea nitrogen, glomerular filtration rate and phenolsulfonphtalein, were performed before and at 8 and 48 weeks after the administration of urokinase. There was marked improvement of proteinuria after UK therapy in patients without deposition of alpha 2-PI in the glomeruli. In contrast, the improvement of proteinuria after UK therapy was not observed in patients with positive deposition of alpha 2-PI in the glomeruli. It was concluded that the administration of UK may be useful for treatment of proteinuria in patients with IgA nephropathy.
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PMID:Significant correlation between the immunofluorescence of alpha 2-plasmin inhibitor in glomeruli and the effects of urokinase therapy in patients with IgA nephropathy. 353 Jan 7

A new method for measuring DNA antibody forming cells (DNA-AFC) using the enzyme-linked immunospot (ELISPOT) assay is described. This method uses enzyme-linked immunosorbent assay (ELISA) techniques applied to cells cultured on DNA-coated plates, which allows visual quantitation of spots representing imprints of specific antibodies from DNA-AFC. Specificity for DNA was confirmed by inhibition studies and lack of reactivity by anti-lysozyme hybridomas. Isotypes of IgG and IgM can be measured using the appropriate antisera in the assay. A study of 16 female (New Zealand black x New Zealand white)F1 ([NZB x NZW]F1) female mice showed significant correlation between age, rising blood urea nitrogen levels, and increasing proteinuria and increasing numbers of DNA-AFC. In contrast, the correlation between circulating antibodies to DNA (ELISA method) and clinical parameters of nephritis was not significant. Both the native DNA ELISPOT and the native DNA ELISA had similar significant linear correlations with age. This is the first report of use of the ELISPOT assay for measurement of DNA-AFC. The DNA-AFC measured by this method were specific and correlated with the presence of clinical nephritis in (NZB x NZW)F1 mice. This method should allow further study on the regulation of DNA-AFC in vitro and in vivo, and will be useful in the investigation of DNA-AFC and cellular mechanisms of autoimmunity.
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PMID:Detection of native and denatured DNA antibody forming cells by the enzyme-linked immunospot assay. A clinical study of (New Zealand black x New Zealand white)F1 mice. 353 Feb 55

Previous studies have demonstrated that N-(3,5-dichlorophenyl)succinimide (NDCPS) is the most nephrotoxic compound among the N-(mono- or dichlorophenyl)succinimides. The purpose of this study was to examine the nephrotoxic potential of the different N-(3,5-dihalophenyl)succinimides (NDHPS) to determine the importance of the halogen species for NDHPS-induced nephrotoxicity. Male Fischer 344 rats were administered a single intraperitoneal injection of an NDHPS (0.4, 0.8, or 1.0 mmol/kg) or vehicle (2.5 ml/kg), and renal function was monitored at 24 and 48 h. NDCPS or N-(3,5-diiodophenyl)succinimide administration produced the greatest nephrotoxic response. Nephrotoxicity was characterized by diuresis, increased proteinuria, glucosuria, increased kidney weight and blood urea nitrogen (BUN) concentration, decreased accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA) by renal cortical slices and proximal tubular necrosis. N-(3,5-Dibromophenyl)succinimide injection produced mild nephrotoxicity, while N-(3,5,-difluorophenyl)succinimide administration did not result in nephrotoxicity. These results indicate that the halogen species can influence the nephrotoxicity produced by the NDHPS. In addition, nephrotoxic potential did not correlate with fungicidal efficacy, which suggests that the nephrotoxic and fungicidal mechanisms of these compounds might be different.
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PMID:Nephrotoxicity of N-(3,5-dihalophenyl)succinimides in Fischer 344 rats. 356 Feb 57

N-(3,5-Dichlorophenyl)succinimide (NDPS), an experimental agricultural fungicide, has been shown to produce selective nephrotoxicity in rats. Previous studies have shown that a metabolite(s) of extrarenal origin contributes to acute NDPS-induced nephrotoxicity. The purpose of this study was to determine if the organic acid transport inhibitor probenecid could modify the renal toxicity produced by NDPS administration. Male Fischer 344 rats were administered a single intraperitoneal (i.p.) injection of probenecid (60, 90 and 120 mg/kg) or 0.9% saline (1.0 ml/kg) followed 30 min later by NDPS (0.4 or 1.0 mmol/kg, i.p.) or sesame oil (2.5 ml/kg, i.p.) Renal function was monitored at 24 h and 48 h. Probenecid (60 mg/kg) did not markedly alter NDPS-induced renal effects on either post-treatment day. However, pretreatment with probenecid (90 or 120 mg/kg) blocked or attenuated the diuresis, increased proteinuria, decreased tetraethylammonium (TEA), uptake, elevation in blood urea nitrogen (BUN) concentration and increased kidney weight produced by NDPS (0.4 mmol/kg) administration. Only increased kidney weight and BUN concentration, and decreased lactate-stimulated p-aminohippurate (PAH) uptake were altered by probenecid (120 mg/kg) pretreatment when NDPS (1.0 mmol/kg) was given. NDPS-induced changes in renal morphology were not prevented by pretreatment with any probenecid dose. These results suggest that at least one nephrotoxic metabolite of NDPS is an organic acid. However, this acidic metabolite might not be the major nephrotoxic metabolite or a precursor to the major nephrotoxic metabolite(s). The identity of these metabolites remains to be determined.
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PMID:The effect of probenecid on acute N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity in the Fischer 344 rat. 356 52

N-(3,5-Dichlorophenyl)succinimide (NDPS), an experimental agricultural fungicide, has been shown to be a selective nephrotoxin in Sprague-Dawley and Fischer 344 rats. Previous studies have demonstrated that a toxic metabolite contributes to or is responsible for acute NDPS-induced nephrotoxicity. The purpose of this study was to investigate the role of glutathione in NDPS-induced renal effects. In 1 set of experiments, male Sprague-Dawley or Fischer 344 rats received a single intraperitoneal (i.p.) injection of NDPS (0.4 or 1.0 mmol/kg) or sesame oil (2.5 ml/kg). Rats were killed at 1, 3, 6 or 24 h, and reduced (GSH) and oxidized (GSSG) glutathione concentrations determined in liver and renal cortex. In both rat strains NDPS (0.4 or 1.0 mmol/kg) administration produced small decreases in GSH concentrations (1 and 3 h) but moderate increases in GSSG concentrations (1 and 3 h) in liver and kidney. At 24 h both GSH and GSSG concentrations were increased, particularly in kidney. In a second set of experiments, rats were pretreated with the glutathione depletor diethyl maleate (DEM) (0.4 ml/kg, i.p.) 1 h prior to NDPS (0.2, 0.4 or 1.0 mmol/kg, i.p.) or sesame oil (2.5 ml/kg, i.p.) administration, and renal function monitored at 24 and 48 h. DEM pretreatment attenuated the increase in urine volume (24 and 48 h), proteinuria, glucosuria, hematuria and elevated blood urea nitrogen (BUN) concentration produced by NDPS (0.4 or 1.0 mmol/kg) in both Sprague-Dawley and Fischer 344 rats. NDPS-induced increases in kidney weight also were generally prevented by DEM pretreatment. Proximal tubular necrosis produced by NDPS administration was reduced by DEM but not prevented. Pretreatment with the cysteine conjugate beta-lyase inhibitor amino-oxyacetic acid (0.5 mmol/kg, i.p.) 1 h prior to NDPS (0.4 or 1.0 mmol/kg) markedly attenuated all NDPS-induced effects on renal function and morphology. These results suggest that glutathione does not play a protective role against NDPS-induced renal effects and that a glutathione or cysteine conjugate of NDPS might contribute to NDPS-induced nephrotoxicity.
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PMID:Role of glutathione in acute N-(3,5-dichlorophenyl) succinimide-induced nephrotoxicity in Sprague-Dawley and Fischer 344 rats. 360 74

The N-phenylsuccinimides are being evaluated as experimental agricultural fungicides. The purpose of this study was to examine the relationship between the electron withdrawing or electron donating properties of phenyl ring substituents on meta-substituted N-phenylsuccinimide (NPS) derivatives and the nephrotoxic potential of the corresponding fungicides. Male Fischer 344 rats were administered a single intraperitoneal injection of a succinimide (0.4 or 1.0 mmol/kg) or vehicle (sesame oil, 2.5 ml/kg), and renal function monitored at 24 and 48 hr. Non-halogen-substituted NPS derivatives produced little evidence of nephrotoxicity at the doses used in this study. Among the meta-halogen derivatives of NPS, N-(3-chlorophenyl)succinimide (NCPS) was the most nephrotoxic. NCPS-induced nephrotoxicity was characterized by diuresis, proteinuria, hematuria, elevated blood urea nitrogen (BUN) concentration, decreased organic ion accumulation and proximal tubular necrosis. However, all renal effects produced by NCPS were mild to moderate. These results suggest that the electron withdrawing or donating property of a functional group is not a good predictor of the nephrotoxic potential for the corresponding fungicide. In addition, lipophilicity did not correlate with nephrotoxic potential for the meta-substituted NPS derivatives evaluated in this study.
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PMID:Structure-nephrotoxicity relationships for meta-substituted N-phenylsuccinimides. 362 73

N-(3,5-Dichlorophenyl)succinimide (NDPS) is an experimental agricultural fungicide which has been shown to be a selective nephrotoxin. The purpose of this study was to determine if a NDPS metabolite contributes to acute NDPS-induced nephrotoxicity. Male Sprague-Dawley or Fischer 344 rats were pretreated with a microsomal enzyme inducer [phenobarbital (PB) or 3-methylcholanthrene (3-MC)] or inhibitor [cobalt chloride (CoCl2) or piperonyl butoxide (PIBX)] followed by a single intraperitoneal injection of NDPS (0.2, 0.4 or 1.0 mmol/kg) or vehicle (sesame oil, 2.5 ml/kg). Renal function was monitored at 24 and 48 h. CoCl2 or PIBX pretreatment reduced NDPS-induced diuresis, proteinuria and hematuria, and reduced the increases seen in the blood urea nitrogen (BUN) concentration and kidney weight. NDPS-induced decreases in organic ion accumulation were not markedly altered by CoCl2 or PIBX pretreatment. PB pretreatment enhanced all NDPS- (0.2 mmol/kg) induced renal effects, while 3-MC pretreatment protected against NDPS-induced diuresis, proteinuria, hematuria, and increases in the BUN concentration observed in both rat strains. Kidney weight and organic ion uptake changes were not substantially different between NDPS-treated rats with or without 3-MC pretreatment. It was concluded that a metabolite(s) contributes to or is responsible for acute NDPS-induced nephrotoxicity and that at least 1 toxic metabolite might be of extrarenal origin.
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PMID:Effect of microsomal enzyme activity modulation on N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity. 362 11


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