Payan J P, Saillenfait A M, Beydon D, Ban M, de Ceaurriz J
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
Toxicology. 1990 Dec 17;65(1-2):223-32. doi: 10.1016/0300-483x(90)90091-t.
Nulliparous female, 10-day and 20-day pregnant rats were injected intraperitoneally with saline or labelled cadmium-metallothionein (109Cd-MTh) at a single dose of 25 or 250 micrograms Cd as cadmium-metallothionein (Cd-MTh)/kg and sacrificed at 24 h. The renal toxicity was manifested by increased 24-h urinary excretion of beta 2-microglobulin (beta 2-m) and the increased number of damaged convoluted proximal tubules at 24 h. The renal excretion of 109Cd and 109Cd content in the maternal liver and kidney and in the foeto-placental unit were determined. The binding of 109Cd to kidney proteins and the level of intracellular metallothionein (MTh) in livers and kidneys were also determined. It was found that the nephrotoxicity of injected Cd-MTh did not differ in nulliparous and 10-day pregnant rats. This result was consistent with the absence of difference in the renal uptake of 109Cd, its binding to kidney proteins and in the content of endogenous MTh in the kidneys between nulliparous and 10-day pregnant rats. In contrast, 20-day pregnant rats exhibited much more nephrotoxicity than nulliparous rats. The most prominent finding in relation to the extreme sensitivity of 20-day pregnant rats was a lower basal level of intracellular MTh in the kidneys and the accumulation of 109Cd in the high molecular weight proteins in the soluble fraction. It is suggested that the decrease of intracellular MTh in the kidneys of 20-day pregnant rats is the reason for the low protection against the renal toxicity of injected Cd-MTh.
未孕雌性大鼠、妊娠10天和20天的大鼠腹腔注射生理盐水或标记的镉 - 金属硫蛋白（109Cd - MTh），单剂量为25或250微克镉（以镉 - 金属硫蛋白（Cd - MTh）计）/千克，并在24小时后处死。肾毒性表现为24小时尿β2 - 微球蛋白（β2 - m）排泄增加以及24小时时受损近曲小管数量增加。测定了母体肝脏、肾脏以及胎儿 - 胎盘单位中109Cd的肾排泄量和109Cd含量。还测定了109Cd与肾脏蛋白质的结合以及肝脏和肾脏中细胞内金属硫蛋白（MTh）的水平。发现注射的Cd - MTh对未孕大鼠和妊娠10天的大鼠的肾毒性没有差异。这一结果与未孕大鼠和妊娠10天的大鼠在109Cd的肾脏摄取、其与肾脏蛋白质的结合以及肾脏中内源性MTh含量方面不存在差异相一致。相比之下，妊娠20天的大鼠比未孕大鼠表现出更强的肾毒性。与妊娠20天大鼠的极端敏感性相关的最显著发现是肾脏中细胞内MTh的基础水平较低以及109Cd在可溶性部分的高分子量蛋白质中积累。提示妊娠20天大鼠肾脏中细胞内MTh的减少是对注射的Cd - MTh肾毒性保护作用低的原因。
