Valentovic M A, Teets V J, Nicoll D, Stern J, Leppla D, Rankin G O
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
Toxicology. 1990 Sep;63(3):327-39. doi: 10.1016/0300-483x(90)90194-l.
N-(3,5-Dichlorophenyl)succinimide (NDPS) is an experimental fungicide which induces renal toxicity. The following study examined the nephrotoxicity induced by NDPS in streptozotocin (STZ) diabetic rats. Male Fischer 344 (F344) rats were injected with 35 mg/kg STZ (i.p.) or citrate buffer. Fourteen days after STZ or citrate buffer injection, the rats (4-6 rats/group) were injected with (0.4 or 1.0 mmol/kg) NDPS or vehicle (sesame oil, 2.5 ml/kg). Kidney weight, blood urea nitrogen (BUN) levels, morphology and renal cortical slice uptake of organic ions was quantitated 48 h after NDPS administration. A 0.4 mmol/kg dose of NDPS induced diuresis, increased kidney weight and a moderate elevation in BUN levels in the normoglycemic group. The 1.0 mmol/kg dose of NDPS produced diuresis, proteinuria, increased kidney weight and a marked increase in BUN levels in the normoglycemic group. The renal cortical slice uptake of p-aminohippurate (PAH) and tetraethylammonium (TEA) was also decreased 48 h after NDPS injection in the normoglycemic group. No alterations in kidney weight, BUN levels, morphology or renal cortical slice uptake of organic ions was observed in the diabetic animals treated with (0.4 or 1.0 mmol/kg) NDPS. The results of this study indicate that the renal toxicity of NDPS was reduced in the diabetic rat.
N-(3,5-二氯苯基)琥珀酰亚胺(NDPS)是一种可诱发肾毒性的实验性杀菌剂。以下研究检测了NDPS对链脲佐菌素(STZ)诱导的糖尿病大鼠的肾毒性。给雄性Fischer 344 (F344)大鼠腹腔注射35 mg/kg STZ或柠檬酸盐缓冲液。在注射STZ或柠檬酸盐缓冲液14天后,给大鼠(每组4 - 6只)注射(0.4或1.0 mmol/kg) NDPS或赋形剂(芝麻油,2.5 ml/kg)。在给予NDPS 48小时后,对肾脏重量、血尿素氮(BUN)水平、形态以及肾皮质切片对有机离子的摄取进行定量分析。0.4 mmol/kg剂量的NDPS在血糖正常组中诱导利尿、增加肾脏重量并使BUN水平适度升高。1.0 mmol/kg剂量的NDPS在血糖正常组中产生利尿、蛋白尿、增加肾脏重量并使BUN水平显著升高。在血糖正常组中,注射NDPS 48小时后,对氨基马尿酸(PAH)和四乙铵(TEA)的肾皮质切片摄取也减少。在用(0.4或1.0 mmol/kg) NDPS治疗的糖尿病动物中,未观察到肾脏重量、BUN水平、形态或肾皮质切片对有机离子摄取的改变。本研究结果表明,NDPS在糖尿病大鼠中的肾毒性降低。