Rankin G O, Beers K W, Teets V J, Nicoll D W, Anestis D K, Brown P I, Wang R T
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
Toxicology. 1994 Mar 11;88(1-3):151-64. doi: 10.1016/0300-483x(94)90117-1.
The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is an established nephrotoxicant in male Fischer 344 rats at i.p. doses of > or = mmol/kg. Since gender differences often exist in the susceptibility to toxicants, the nephrotoxic potential of NDPS was examined in female Fischer 344 rats. Rats (4-5/group) were administered NDPS (0.1, 0.2, 0.4, or 1.0 mmol/kg, i.p.) or vehicle (sesame oil, 2.5 ml/kg) and renal function monitored for 48 h. At a dose of 0.1 mmol/kg, NDPS had no effect on renal function. However, administration of NDPS at a dose of 0.2 or 0.4 mmol/kg resulted in marked nephrotoxicity characterized by diuresis, increased proteinuria, glucosuria, hematuria, elevated blood urea nitrogen (BUN) concentration and kidney weight, decreased organic ion accumulation and proximal tubular necrosis. NDPS treatment of 1.0 mmol/kg resulted in oliguric renal failure rather than polyuric renal failure in 3 of 4 rats. Proximal tubular damage was observed primarily in the S3 segment of the proximal tubule in NDPS-treated female rats, while in male rats the S1 and S2 segments are the initial renal targets. These results demonstrate that female Fischer 344 rats are more susceptible to NDPS nephrotoxicity than male Fischer 344 rats and that the site of the renal lesion is gender dependent.
农业杀菌剂N-(3,5-二氯苯基)琥珀酰亚胺(NDPS)对雄性Fischer 344大鼠腹腔注射剂量≥mmol/kg时是一种已确定的肾毒性物质。由于对毒物的易感性往往存在性别差异，因此对雌性Fischer 344大鼠的NDPS肾毒性潜力进行了研究。将大鼠(每组4-5只)给予NDPS(0.1、0.2、0.4或1.0 mmol/kg，腹腔注射)或溶剂(芝麻油，2.5 ml/kg)，并监测肾功能48小时。剂量为0.1 mmol/kg时，NDPS对肾功能无影响。然而，以0.2或0.4 mmol/kg的剂量给予NDPS会导致明显的肾毒性，其特征为多尿、蛋白尿增加、糖尿、血尿、血尿素氮(BUN)浓度和肾脏重量升高、有机离子蓄积减少和近端肾小管坏死。1.0 mmol/kg的NDPS处理导致4只大鼠中有3只出现少尿性肾衰竭而非多尿性肾衰竭。在接受NDPS处理的雌性大鼠中，近端肾小管损伤主要发生在近端小管的S3段，而在雄性大鼠中，S1和S2段是最初的肾脏靶标。这些结果表明，雌性Fischer 344大鼠比雄性Fischer 344大鼠对NDPS肾毒性更敏感，并且肾损伤部位具有性别依赖性。
