Darnerud P O, Olsson L
Department of Toxicology, Uppsala University, Sweden.
Toxicol Lett. 1990 Jun;52(1):63-72. doi: 10.1016/0378-4274(90)90166-j.
In order to assess the potential hazard of the nephrotoxic compound S-1,2-dichlorovinyl-L-cysteine (DCVC) during gestation, studies on its disposition and degenerative effects were performed in pregnant mice. In late gestation, binding of 14C-DCVC (spec. act. 1.01 microCi/mumol) equivalents was observed by autoradiography in the inner cortex of the kidney, in the liver and gastrointestinal tract of the fetuses. The uptake of radioactivity in the fetal kidney increased from day 13 to day 18 of gestation when measured by liquid scintillation. When fetuses were injected in utero, a distinct binding of 14C-DCVC was present in the kidney cortex. This fact suggests that bioactivation occurs in situ, as the reactive products are not likely to be transported far from their site of formation. The concentration of radioactivity in the fetal kidney at day 18 of gestation was about 10% of that found in the maternal kidney. Limiting factors for fetal kidney uptake may be both transplacental transfer, and renal bioactivation and transport activities. No distinct histopathological changes in the fetal kidney were observed when a nephrotoxic dose (25 mg/kg) of DCVC was given to the dam. These results suggest that the fetal kidney during late gestation is able to activate and bind DCVC. However, the degree of fetal binding seems too low to cause any visible histopathological effects.
为了评估肾毒性化合物S-1,2-二氯乙烯基-L-半胱氨酸(DCVC)在妊娠期的潜在危害,在怀孕小鼠中进行了关于其处置和退化作用的研究。在妊娠晚期,通过放射自显影观察到14C-DCVC(比活度为1.01微居里/微摩尔)等效物在胎儿的肾内皮质、肝脏和胃肠道中结合。通过液体闪烁法测量,胎儿肾脏中放射性的摄取在妊娠第13天至第18天增加。当在子宫内给胎儿注射时,14C-DCVC在肾皮质中有明显的结合。这一事实表明原位发生了生物活化,因为反应产物不太可能从其形成部位远距离转运。妊娠第18天胎儿肾脏中的放射性浓度约为母体肾脏中浓度的10%。胎儿肾脏摄取的限制因素可能是胎盘转运以及肾脏的生物活化和转运活性。当给母鼠给予肾毒性剂量(25毫克/千克)的DCVC时,未观察到胎儿肾脏有明显的组织病理学变化。这些结果表明,妊娠晚期的胎儿肾脏能够活化并结合DCVC。然而,胎儿结合的程度似乎太低,不会引起任何可见的组织病理学效应。