Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-(3,5-Dichlorophenyl)succinimide (NDPS) is an agricultural fungicide which has been shown to induce acute tubular necrosis. The purpose of the present study was to determine if creatinine clearance was altered early in the development of NDPS nephrotoxicity. This study also examined the effect of autacoid modulation on the renal effects induced by NDPS and two metabolites of NDPS, N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (NDHSA). In one set of experiments, male Fischer 344 rats (4 rats/group) were administered a single intraperitoneal (i.p.) injection of NDPS (1.0 mmol/kg) or vehicle and creatinine clearance was determined at 3 and 6 h post-treatment. NDPS administration resulted in a marked decrease in creatinine clearance at both time points. In a second set of experiments, rats (4-8 rats/group) were pretreated with the cyclooxygenase inhibitor indomethacin (3.0 or 5.0 mg/kg, i.p.) or the thromboxane synthase inhibitor dazmegrel (20 mg/kg, i.p.) 1 h before the i.p. administration of NDPS (0.2 or 0.4 mmol/kg), NDHS (0.05 or 0.1 mmol/kg), NDHSA (0.05 or 0.1 mmol/kg) or vehicle. Indomethacin pretreatment potentiated the nephrotoxic potential of NDPS and its two metabolites, while dazmegrel pretreatment attenuated NDPS nephrotoxicity without marked effects on NDHS or NDHSA nephropathy. These results indicate that renal hemodynamic changes occur early in the development of NDPS nephrotoxicity and that autacoids are important modulators of NDPS- and NDPS metabolite-induced renal effects.
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PMID:Effect of autacoid modulation on N-(3,5-dichlorophenyl)succinimide (NDPS) and NDPS metabolite nephrotoxicity. 177 40

N-(3,5-Dichlorophenyl)succinimide (NDPS) is an agricultural fungicide which induces acute tubular necrosis as its primary toxicity. Two NDPS metabolites, N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (NDHSA) previously have been shown to be more potent nephrotoxicants than NDPS. In addition, buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, was found to attenuate NDPS-induced nephrotoxicity. The purpose of this study was to examine the effects of BSO pretreatment on NDHS- and NDHSA-induced nephrotoxicity. Male Fischer-344 rats (4 rats/group) were administered intraperitoneally (i.p.) BSO (890 mg/kg) 2 h before NDHS or NDHSA (0.1 or 0.2 mmol/kg, i.p.) or vehicle (sesame oil, 2.5 ml/kg), and renal function monitored at 24-h intervals for 48 h. BSO pretreatment markedly attenuated NDHSA (0.1 or 0.2 mmol/kg)-induced effects on the renal functional parameters monitored. BSO pretreatment also markedly reduced NDHS (0.1 mmol/kg)-induced renal effects. However, NDHS (0.2 mmol/kg) nephrotoxicity was attenuated to a lesser extent than NDHS (0.1 mmol/kg) nephropathy. These results indicate that glutathione is an important mediator of NDPS metabolite nephrotoxicity and suggests that BSO did not attenuate NDPS nephropathy by inhibiting NDPS biotransformation to NDHS or NDHSA.
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PMID:Effect of buthionine sulfoximine on N-(3,5-dichlorophenyl)-2-hydroxysuccinimide and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid nephrotoxicity. 188 89

The nephrotoxic potential of N-(3,5-dichlorophenyl)succinimide (NDPS) was examined, in male Fischer-344 rats. Rats were administered NDPS (0.1, 0.2, 0.4 or 1.0 mmol/kg intraperitoneally (i.p.) or sesame oil (2.5 ml/kg, i.p.), and renal function was monitored at 24 and 48 h. NDPS (0.1 mmol/kg) stimulated organic ion uptake at 48 h. NDPS (0.2 mmol/kg) produced diuresis but did not alter blood urea nitrogen (BUN), kidney weight or organic ion uptake by renal cortical slices at 48 h. High-dose NDPS (0.4 and 1.0 mmol/kg) administration produced diuresis, decreased accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA), increased BUN and kidney weight and caused acute tubular necrosis. At 24 h, NDPS (0.2 mmol/kg) decreased uptake of PAH and TEA and tended to increase BUN. These results are similar to previous reports of NDPS-induced nephrotoxicity in Sprague-Dawley rats and suggest that either rat model would be suitable for future studies on the mechanism(s) of NDPS-induced nephropathy.
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PMID:N-(3,5-Dichlorophenyl)succinimide nephrotoxicity in the Fischer-344 rat. 397 35