Abstract：
: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.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Rankin GO,Valentovic MA,Teets VJ,Nicoll DW,Anestis DK,Brown PIdoi
10.1016/0300-483x(91)90007-nsubject
Has Abstractpub_date
1991-01-01 00:00:00pages
327-44issue
3eissn
0300-483Xissn
1879-3185pii
0300-483X(91)90007-Njournal_volume
70pub_type
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