Maitani T, Saito Y, Suzuki K T
Toxicology. 1985 Oct;37(1-2):27-38. doi: 10.1016/0300-483x(85)90110-6.
The critical concentration of cadmium (Cd) in the kidney after acute administration of Cd-cysteine (Cys) is 10 micrograms/g wet wt in whole kidney and is equal to that following Cd-thionein (Th) injection. This fact suggests that the nephrotoxicity of Cd-Th may be due to the Cd ions liberated from Cd-Th. To clarify the mechanism of the nephrotoxicity, the subcellular distribution of Cd injected as Cd-Cys was determined between supernatant and sediment fractions. Renal Cd level observed at 4 h increased with dose, but the Cd concentration in the supernatant fraction was kept almost constant at higher doses. Renal dysfunction measured by urinary protein and glucose levels was seen at the higher doses. This suggested that Cd in the sediment fraction of the kidney homogenates may be the ultimate cause for the nephrotoxicity of Cd-Cys. The sedimental Cd was eliminated from the kidney by 24 h. Much of the Cd found in the supernatant fraction was bound to high-molecular-weight proteins (HMWP) at 4 h, and almost all Cd ions were found to be bound to metallothionein at 24 h. Therefore, the HMWP-bound Cd in the supernatant fraction also may be a cause for the renal dysfunction. It is concluded that in addition to the HMWP-bound Cd in the supernatant fraction, CD distribution into the sediment fraction should be considered as a factor in causing nephrotoxicity after Cd-Cys and possibly Cd-Th administration.
急性给予镉 - 半胱氨酸（Cd - Cys）后，肾脏中镉（Cd）的临界浓度在整个肾脏中为10微克/克湿重，与注射镉 - 金属硫蛋白（Cd - Th）后的浓度相当。这一事实表明，Cd - Th的肾毒性可能归因于从Cd - Th中释放出的镉离子。为阐明肾毒性机制，对以Cd - Cys形式注射的镉在亚细胞水平上在上清液和沉淀组分之间的分布进行了测定。4小时时观察到的肾脏镉水平随剂量增加，但在上清液组分中，较高剂量时镉浓度几乎保持恒定。在较高剂量下出现了通过尿蛋白和葡萄糖水平衡量的肾功能障碍。这表明肾脏匀浆沉淀组分中的镉可能是Cd - Cys肾毒性的最终原因。沉淀中的镉在24小时内从肾脏中消除。上清液组分中发现的大部分镉在4小时时与高分子量蛋白质（HMWP）结合，在24小时时几乎所有镉离子都与金属硫蛋白结合。因此，上清液组分中与HMWP结合的镉也可能是肾功能障碍的一个原因。得出的结论是，除了上清液组分中与HMWP结合的镉外，镉在沉淀组分中的分布也应被视为Cd - Cys以及可能的Cd - Th给药后导致肾毒性的一个因素。
