Itoh N, Fujita Y, Nakanishi H, Kawai Y, Mayumi T, Hwang G S, Min K, Onosaka S, Muto N, Tanaka K
Faculty of Pharmaceutical Sciences, Osaka University, Suita, Japan.
J Toxicol Sci. 1996 Feb;21(1):19-27. doi: 10.2131/jts.21.19.
The toxicological significance of the placental metallothionein (MT) was studied from the viewpoint of cadmium (Cd) intoxication. The Cd concentration was higher in the placenta than the kidneys until 8 hr after a single injection of 109CdCl2, but was very low after administration of 109Cd-MT. Compared with lower doses, fetal Cd began to increase at the dose of 2 mg/kg. Alkaline phosphatase activity in the placenta was significantly decreased, and dead fetuses appeared at this dose. The MT concentration was not increased by the Cd injection but the ratio of Cd/Zn in MT increased proportionally to the dose up to 2 mg/kg. MT was detected in the placenta during all stages of pregnancy, and its concentration was higher in the earlier stage. The metal bound to MT was mainly Zn, and very little Cu was bound. In the mice that became pregnant after 109Cd accumulation, redistribution of 109Cd was not observed. MT-I and -II in the placenta were identified by column chromatography and immunoblotting methods. These findings suggest that the placental MT might play a protective role against Cd toxicity by trapping of the metal.
从镉(Cd)中毒的角度研究了胎盘金属硫蛋白(MT)的毒理学意义。单次注射109CdCl2后8小时内,胎盘中的镉浓度高于肾脏,但注射109Cd-MT后镉浓度非常低。与较低剂量相比,当剂量达到2mg/kg时,胎儿体内的镉开始增加。此时胎盘碱性磷酸酶活性显著降低,并出现死胎。注射镉后MT浓度未增加,但MT中Cd/Zn的比例与剂量成正比增加,直至2mg/kg。在整个孕期都能在胎盘中检测到MT,且其浓度在早期较高。与MT结合的金属主要是锌,结合的铜很少。在蓄积109Cd后怀孕的小鼠中,未观察到109Cd的重新分布。通过柱色谱法和免疫印迹法鉴定了胎盘中的MT-I和-II。这些发现表明,胎盘MT可能通过捕获金属对镉毒性起到保护作用。