McQuaid A, Lamand M, Mason J
Biochemistry Department, Trinity College, Dublin University, Ireland.
J Inorg Biochem. 1994 Feb 15;53(3):205-18. doi: 10.1016/0162-0134(94)80005-7.
The intraperitoneal administration of tetrathiotungstate to rats (6-17.4 mg W/Kg BW) caused profound changes in copper metabolism in both normal rats and in rats pretreated with copper. Plasma copper associated with albumin increased, liver copper, particularly cytosol copper, was depleted, and biliary excretion was increased. There was also a movement of copper to higher molecular weight proteins in both liver cytosol and bile. In contrast to penicillamine, tetrathiotungstate did not increase liver cytosolic apometallothionein levels and reduced the rise provoked by copper. Metallothionein-bound copper was removed. Ceruloplasmin oxidase activity was inhibited and there was evidence for increased movement of copper into subcellular organelles, probably lysosomes. It is concluded that tetrathiotungstate has a genuine "decoppering" effect and could be considered as an alternative to thiomolybdates in the treatment of copper storage diseases.
给大鼠腹腔注射四硫代钨酸盐(6 - 17.4毫克钨/千克体重),会使正常大鼠和预先用铜处理过的大鼠的铜代谢发生深刻变化。与白蛋白结合的血浆铜增加,肝脏铜,尤其是胞质铜减少,胆汁排泄增加。肝脏胞质和胆汁中的铜也向高分子量蛋白质转移。与青霉胺不同,四硫代钨酸盐不会增加肝脏胞质脱金属硫蛋白水平,反而会降低铜引发的脱金属硫蛋白水平升高。与金属硫蛋白结合的铜被去除。铜蓝蛋白氧化酶活性受到抑制,有证据表明铜向亚细胞器(可能是溶酶体)的转运增加。结论是,四硫代钨酸盐具有真正的“除铜”作用,在治疗铜贮积病方面可被视为硫代钼酸盐的替代品。