Daston G P, Rehnberg B F, Carver B, Kavlock R J
Department of Biological Sciences, University of Wisconsin, Milwaukee 53201.
Fundam Appl Toxicol. 1988 Oct;11(3):401-15. doi: 10.1016/0272-0590(88)90105-4.
Nitrofen and ethylenethiourea (ETU), agents known to prenatally induce hydronephrosis in rats, were assessed for their effects on postnatal renal functional maturation. Both were given by gavage to pregnant Sprague-Dawley rats on Gestation Day 11. Nitrofen was given at concentrations of 50 or 100 mg/kg, and ETU at 20, 40, or 60 mg/kg. Renal function was examined in the offspring from birth until after weaning, the period of renal functional maturation in the rat. Maximal urine concentrating ability was measured after DDAVP (desmopressin acetate, a vasopressin analog) challenge or water deprivation. Proximal tubule transport was measured in renal cortical slices. Various urinary parameters were measured. Both prenatal nitrofen and ETU exposure caused a large number of neonatal deaths at the high dose, and hydronephrosis was observed. The severity of the lesion increased with age. Hydronephrotic animals were deficient in urine concentrating ability, which became more pronounced after weaning. A few other urinary parameters were altered, but cortical function appeared to be unaffected. Rats prenatally exposed to nitrofen, but with apparently normal kidneys, were significantly compromised in their ability to produce a concentrated urine in response to DDAVP challenge, on Postnatal Days (PDs) 6 and 14. By PD 30, they were not different from controls in urine concentrating response. Rats prenatally exposed to the higher doses of ETU, but with grossly normal kidneys, had significantly decreased plasma clearances of certain electrolytes early in life, but by PD 27, they were not different from controls. Proximal tubule transport of PAH was increased on PD 7 in ETU-exposed pups, but this effect did not persist.
已知在大鼠孕期可诱导肾积水的除草醚和乙烯硫脲（ETU），被评估了它们对产后肾功能成熟的影响。在妊娠第11天，通过灌胃将这两种物质给予怀孕的斯普拉格-道利大鼠。除草醚的给药浓度为50或100mg/kg，ETU的给药浓度为20、40或60mg/kg。对出生至断奶后的子代进行肾功能检查，此为大鼠肾功能成熟的时期。在给予醋酸去氨加压素（一种抗利尿激素类似物）刺激或禁水后测量最大尿浓缩能力。在肾皮质切片中测量近端小管转运。测量各种尿液参数。产前暴露于除草醚和ETU均导致高剂量组出现大量新生死亡，并观察到肾积水。病变严重程度随年龄增加。肾积水动物的尿浓缩能力不足，断奶后更为明显。其他一些尿液参数发生改变，但皮质功能似乎未受影响。产前暴露于除草醚但肾脏外观正常的大鼠，在出生后第6天和第14天对醋酸去氨加压素刺激产生浓缩尿的能力显著受损。到出生后第30天，它们在尿浓缩反应方面与对照组无差异。产前暴露于较高剂量ETU但肾脏大体正常的大鼠，在生命早期某些电解质的血浆清除率显著降低，但到出生后第27天，它们与对照组无差异。暴露于ETU的幼崽在出生后第7天PAH的近端小管转运增加，但这种作用未持续。
