EFFECTS OF SODIUM-SULFATE ON ACUTE N-(3,5-DICHLOROPHENYL)SUCCINIMIDE (NDPS) NEPHROTOXICITY IN THE FISCHER-344 RAT

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) in duces acute polyuric renal failure in rats. Results of previous studie s have suggested that NDPS may induce nephrotoxicity via conjugates of NDPS metabolites. Thus, the purpose of this study was to examine if a dministered sodium sulfate could alter NDPS nephrotoxicity. Male Fisch er 344 rats (four rats per group) were administered a single intraperi toneal (i.p.) injection of sodium sulfate (0.035, 0.07, 0.35 or 3.5 mm ol/kg) or sodium chloride (7.0 mmol/kg) 20 min before NDPS (0.2, 0.4 o r 0.8 mmol/kg) or NDPS vehicle (sesame oil, 2.5 ml/kg) and renal funct ion monitored at 24 and 48 h. High dose sodium sulfate (3.5 mmol/kg) m arkedly attenuated NDPS nephrotoxicity, while sodium chloride had no e ffect on NDPS-induced renal effects. NDPS nephrotoxicity was also atte nuated by a pretreatment dose of 0.35 mmol/kg sodium sulfate, while 0. 07 mmol/kg sodium sulfate pretreatment potentiated NDPS 0.2 mmol/kg to produce nephrotoxicity without markedly attenuating NDPS 0.4 mmol/kg to induce renal effects. A dose of 0.035 mmol/kg sodium sulfate did no t potentiate NDPS 0.2 mmol/kg to induce nephrotoxicity. These results suggest that sulfate conjugates of NDPS metabolites might contribute t o NDPS nephrotoxicity. (C) 1997 Elsevier Science Ireland Ltd.