Discrepancy between the nephrotoxic potencies of cadmium-metallothionein and cadmium chloride and the renal concentration of cadmium in the proximal convoluted tubules.
Discrepancy between the nephrotoxic potencies of cadmium-metallothionein and cadmium chloride and the renal concentration of cadmium in the proximal convoluted tubules.
复制标题
镉金属硫蛋白和氯化镉的肾毒性效力与近曲小管中镉的肾浓度之间的差异。
DOI：
10.1006/taap.1995.1021
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Klaassen,CD
中科院分区：
文献类型：
--
作者：
Dorian,C;Gattone2nd,VH;Klaassen,CD
急性接触无机镉会产生肝毒性，但不会造成肾损伤。相反，长期接触镉会产生肾毒性作用。然而，单次注射与金属硫蛋白结合的镉 (CdMT) 会产生与长期接触镉相似的肾毒性。一般认为 CdMT 具有肾毒性，因为分布到肾脏的 CdMT 多于 CdCl2。为了检验这一假设，比较了小鼠静脉注射 CdMT 和 CdCl2 后 Cd 的毒性作用和分布。 CdMT 增加尿中葡萄糖和蛋白质的排泄，表明肾损伤。当剂量低至 0.2 mg Cd/kg 时，就会出现这种功能障碍。相比之下，即使剂量高达 3 mg Cd/kg，CdCl2 给药也不会改变肾功能。 CdMT 几乎仅分布到肾脏，而 CdCl2 优先分布到肝脏。然而，给予 CdCl2 后，肾脏中也发现了高浓度的 Cd。事实上，施用高但非肾毒性剂量的 CdCl2 后的肾 Cd 浓度等于或高于注射肾毒性剂量的 CdMT 后获得的肾 Cd 浓度。使用 0.3 mg Cd/kg 作为 CdMT 和 3 mg Cd/kg 作为 CdCl2 的光学显微镜放射自显影研究表明，来自 CdMT 的 Cd 优先分布到近端小管的曲段（S1 和 S2），而来自 CdCl2 的 Cd 平均分布到近端小管的各个段（曲段和直段）。然而，CdCl2 后肾毒性部位（近曲小管）的 Cd 浓度高于 CdMT 给药后。发现 CdCl2 后近端细胞的顶端和基底部分的 Cd 浓度高于 CdMT 给药后的 Cd 浓度。因此，CdMT具有肾毒性而CdCl2没有肾毒性的原因并不是因为CdMT后靶细胞中的Cd浓度高于CdCl2施用后的浓度。
Acute exposure to inorganic cadmium produces hepatotoxicity, but no renal injury. In contrast, chronic exposure to Cd produces nephrotoxic effects. However, a single injection of cadmium bound to metallothionein (CdMT) can produce nephrotoxicity similar to that seen with chronic exposure to Cd. It is generally thought that CdMT is nephrotoxic because more CdMT than CdCl2distributes to the kidney. To test this hypothesis, the toxic effects and distribution of Cd were compared after iv injection of CdMT and CdCl2to mice. CdMT increased urinary excretion of glucose, and protein indicating renal injury. This dysfunction occurred with dosages as low as 0.2 mg Cd/kg. In contrast, renal function was unaltered by CdCl2administration, even at dosages as high as 3 mg Cd/kg. CdMT distributed almost exclusively to the kidney, whereas CdCl2preferentially distributed to the liver. However, a high concentration of Cd was also found in the kidneys after CdCl2administration. In fact, the renal Cd concentration after administration of a high but nonnephrotoxic dose of CdCl2was equal to or higher than that obtained after injection of nephrotoxic doses of CdMT. Light microscopic autoradiography studies, using 0.3 mg Cd/kg as CdMT and 3 mg Cd/kg as CdCl2, indicated that Cd from CdMT preferentially distributed to the convoluted segments (S1 and S2) of the proximal tubules, whereas Cd from CdCl2distributed equally to the various segments (convoluted and straight) of the proximal tubules. However, the concentration of Cd at the site of nephrotoxicity, the proximal convoluted tubules, was higher after CdCl2than after CdMT administration. A higher Cd concentration in both apical and basal parts of the proximal cells was found after CdCl2than after CdMT administration. Therefore, the reason why CdMT is nephrotoxic and CdCl2is not nephrotoxic is not due to a higher concentration of Cd in the target cells after CdMT than after CdCl2administration.