3,5-二氯苯胺诱导的Sprague-Dawley大鼠肾毒性

3,5-Dichloroaniline-induced nephrotoxicity in the Sprague-Dawley rat.

作者信息

Rankin G O, Yang D J, Teets V J, Lo H H, Brown P I

出版信息

Toxicol Lett. 1986 Feb;30(2):173-9. doi: 10.1016/0378-4274(86)90100-1.

Abstract

The nephrotoxic potential of 3,5-dichloroaniline (DCA) was examined in male Sprague-Dawley rats. Rats were administered DCA (0.4, 0.8 or 1.0 mmol/kg, i.p.), or 0.9% saline (1.0 ml/kg, i.p.), and renal function was monitored at 24 and 48 h. DCA (0.4 mmol/kg) administration did not produce evidence of nephrotoxicity. However, DCA (0.8 mmol/kg) administration decreased urine volume and osmolality, increased proteinuria, elevated the blood urea nitrogen (BUN) concentration and decreased basal and lactate-stimulated p-aminohippurate (PAH) accumulation. Three of 4 rats receiving DCA (1.0 mmol/kg) died prior to 48 h postinjection. Incubation of renal cortical slices with DCA resulted in decreased PAH and tetraethylammonium (TEA) uptake when DCA concentrations of 10(-6) M or greater were used. These results indicate that DCA is nephrotoxic to Sprague-Dawley rats when administered in a dose of 0.8 mmol/kg or higher and is capable of altering organic ion transport in vitro.

摘要

在雄性斯普拉格-道利大鼠中检测了3,5-二氯苯胺（DCA）的肾毒性潜力。给大鼠腹腔注射DCA（0.4、0.8或1.0 mmol/kg）或0.9%生理盐水（1.0 ml/kg），并在24小时和48小时监测肾功能。给予DCA（0.4 mmol/kg）未产生肾毒性证据。然而，给予DCA（0.8 mmol/kg）会减少尿量和尿渗透压，增加蛋白尿，提高血尿素氮（BUN）浓度，并降低基础和乳酸刺激的对氨基马尿酸（PAH）蓄积。4只接受DCA（1.0 mmol/kg）的大鼠中有3只在注射后48小时前死亡。当使用浓度为10^(-6) M或更高的DCA孵育肾皮质切片时，会导致PAH和四乙铵（TEA）摄取减少。这些结果表明，以0.8 mmol/kg或更高剂量给药时，DCA对斯普拉格-道利大鼠具有肾毒性，并且能够在体外改变有机离子转运。