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)

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

We have previously reported that phenobarbital (PB) pretreatment enhances and piperonyl butoxide (PIBX) pretreatment or cobalt chloride (CoCl2) pretreatment decreases the nephrotoxicity induced by the model nephrotoxicant N-(3,5-dichlorophenyl)succinimide (NDPS) in the Fischer 344 rat. The objective of this study was to determine the effect of a microsomal enzyme inducer (PB) or microsomal enzyme inhibitor (PIBX or CoCl2) on a single intraperitoneal (i.p.) injection of N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS, 0.05, 0.1 or 0.2 mmol/kg), a nephrotoxicant metabolite of NDPS, or vehicle (sesame oil, 2.5 ml/kg). Renal function was monitored at 24 and 48 h post-NDHS for PB pretreated rats and at 24 h only for PIBX and CoCl2 pretreated rats, due to lethality at 48 h in PIBX pretreated rats. PB pretreatment potentiated the renal toxicity induced by a non-toxic dose of NDHS (0.05 mmol/kg), inducing diuresis and elevated proteinuria, hematuria, glucosuria, blood urea nitrogen (BUN) concentration and kidney weight. PB pretreatment also enhanced some monitored renal effects of a toxic dose (0.1 mmol/kg) of NDHS, including reduced organic ion transport by renal cortical slices. PIBX and CoCl2 pretreatments did not markedly affect the increased kidney weight, proteinuria, glucosuria, BUN concentration or altered organic ion transport induced by NDHS (0.2 mmol/kg) treatment. We conclude that PB potentiates NDHS-induced nephrotoxicity via a mechanism not influenced by CoCl2 or PIBX.
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PMID:Effect of microsomal enzyme modulators on N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS)-induced nephrotoxicity in the Fischer 344 rat. 826 34

Inhibition of cytochrome P-450 (CYP450) enzymes with cobalt chloride (CoCl2) prevented hypertension, organ hypertrophy, and renal injury induced by DOCA and salt (1% NaCl) in uninephrectomized (UNx) rats. Systolic blood pressure (SBP) rose to 193 +/- 6 mmHg by day 21 from control levels of 150 +/- 7 mmHg in response to DOCA-salt treatment, a rise that was prevented by CoCl2 (24 mg. kg-1. 24 h-1). The effects of DOCA-salt treatment, which increased protein excretion to 88.3 +/- 6.9 mg/24 h on day 21 from 9.0 +/- 1.1 mg/24 h on day 3, were prevented by CoCl2. CoCl2 also attenuated the renal and left ventricular hypertrophy and the increase in media-to-lumen ratio in hypertensive rats. DOCA-salt treatment increased excretion of endothelin (ET)-1 from 81 +/- 17 to 277 +/- 104 pg. 100 g body wt-1. 24 h-1 associated with a fourfold increase in 20-hydroxyeicosatetraenoic acid (20-HETE) excretion from 3.0 +/- 1.1 to 12.2 +/- 1.9 ng. 100 g body wt-1. 24 h-1 (days 3 vs. 21). CoCl2 blunted these increases by 58 and 72%, respectively. In aortic rings pulsed with [3H]thymidine, ET-1 increased its incorporation. Dibromododec-11-enoic acid, an inhibitor of 20-HETE synthesis, attenuated ET-1-induced increases in [3H]thymidine incorporation. We distinguished effects of CoCl2 acting via CO generation vs. suppression of CYP450-arachidonic acid metabolism by treating UNx-salt-DOCA rats with 1-aminobenzotriazole (ABT), which suppresses CYP450 enzyme activity, and compared these results to those produced by CoCl2. ABT reduced hypertension, as did CoCl2. Unlike CoCl2, ABT did not prevent organ hypertrophy and proteinuria, suggesting that these effects were partially related to CO formation. Blockade of the ETA receptor with BMS-182874 reduced SBP, organ hypertrophy, and proteinuria, indicating the importance of ET-initiated abnormalities to the progression of lesions in UNx-salt-DOCA.
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PMID:Endothelin-1 and CYP450 arachidonate metabolites interact to promote tissue injury in DOCA-salt hypertension. 1007 Jan 37