Rankin G O, Hong S K, Valentovic M A, Beers K W, Anestis D K, Nicoll D W, Ball J G, Brown P I
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25704-9388, USA.
Toxicology. 1997 Nov 21;123(1-2):1-13. 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.
农用杀菌剂N-(3,5-二氯苯基)琥珀酰亚胺(NDPS)可诱发大鼠急性多尿性肾衰竭。先前的研究结果表明，NDPS可能通过其代谢产物的共轭物诱发肾毒性。因此，本研究旨在探讨给予硫酸钠是否能改变NDPS的肾毒性。雄性Fischer 344大鼠(每组4只)在给予NDPS(0.2、0.4或0.8 mmol/kg)或NDPS溶媒(芝麻油，2.5 ml/kg)前20分钟，腹腔注射硫酸钠(0.035、0.07、0.35或3.5 mmol/kg)或氯化钠(7.0 mmol/kg)，并在24小时和48小时监测肾功能。高剂量硫酸钠(3.5 mmol/kg)显著减轻了NDPS的肾毒性，而氯化钠对NDPS诱导的肾脏效应没有影响。0.35 mmol/kg硫酸钠预处理剂量也减轻了NDPS的肾毒性，而0.07 mmol/kg硫酸钠预处理使NDPS 0.2 mmol/kg产生肾毒性，同时又没有显著减轻NDPS 0.4 mmol/kg诱导的肾脏效应。0.035 mmol/kg硫酸钠剂量不会使NDPS 0.2 mmol/kg诱发肾毒性。这些结果表明，NDPS代谢产物的硫酸盐共轭物可能与NDPS的肾毒性有关。
