Effects of sodium sulfate on acute N-(3,5-dichlorophenyl)succinimide (NDPS) nephrotoxicity in the Fischer 344 rat

• Published in: Toxicology (Amsterdam) 1997-11, Vol.123 (1-2), p.1-13
• Main Authors: Rankin, Gary O, Hong, Suk K, Valentovic, Monica A, Beers, Kelly W, Anestis, Dianne K, W. Nicoll, Derek, Ball, John G, Brown, Patrick I
• Format: Article
• Language: English
• Subjects: Animals; Bioactivation; Biological and medical sciences; Biotransformation - drug effects; Blood Urea Nitrogen; Diuresis - drug effects; Drug Synergism; Fungicides; Fungicides, Industrial - metabolism; Fungicides, Industrial - toxicity; Kidney - drug effects; Kidney - metabolism; Male; Medical sciences; Nephrotoxicity; Organ Size - drug effects; p-Aminohippuric Acid - metabolism; Pesticides, fertilizers and other agrochemicals toxicology; Proteinuria - urine; Rats; Rats, Inbred F344; Sodium Chloride - pharmacology; Succinimides - metabolism; Succinimides - toxicity; Sulfates - metabolism; Sulfates - pharmacology; Sulfates - therapeutic use; Sulfation; Tetraethylammonium - metabolism; Toxicology; Urine
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(97)00097-8

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) induces acute polyuric renal failure in rats. Results of previous studies have suggested that NDPS may induce nephrotoxicity via conjugates of NDPS metabolites. Thus, the purpose of this study was to examine if administered sodium sulfate could alter NDPS nephrotoxicity. Male Fischer 344 rats (four rats per group) were administered a single intraperitoneal (i.p.) injection of sodium sulfate (0.035, 0.07, 0.35 or 3.5 mmol/kg) or sodium chloride (7.0 mmol/kg) 20 min before NDPS (0.2, 0.4 or 0.8 mmol/kg) or NDPS vehicle (sesame oil, 2.5 ml/kg) and renal function monitored at 24 and 48 h. High dose sodium sulfate (3.5 mmol/kg) markedly attenuated NDPS nephrotoxicity, while sodium chloride had no effect on NDPS-induced renal effects. NDPS nephrotoxicity was also attenuated 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 not potentiate NDPS 0.2 mmol/kg to induce nephrotoxicity. These results suggest that sulfate conjugates of NDPS metabolites might contribute to NDPS nephrotoxicity.