Effects of Thiosulfydryl Substances on the Metabolism of Heavy Metals

被带入组织的重金属在器官之间运输，迟早会被排出体外。在以往的研究中，我们发现硫代磺酸类物质在降低重金属的毒性和清除体内相关金属方面发挥着重要作用。研究了新合成的硫代半胱胺(TC)、S-乙酰硫代半胱胺(ATC)和硫代牛磺酸(TT)对组织和尿中甲基汞(MM)或镉(Cd)代谢的解毒作用。在体外实验中，TC能从MM预处理的组织中释放出40%~90%的MM，添加MM的MM也能从TC预孵育的组织中释放出来。但在后一次实验中，预孵育100min后，释放作用减弱。Cd组大鼠肝脏中Cd含量、上清液/残留物中Cd含量及蛋白质组分中Cd含量均未见明显变化。体内实验：经MM处理的小鼠在不同条件下给药，单独给药后尿汞含量略有增加，肾汞含量略有下降，但与谷胱甘肽、半胱胺或脂肪混合给药时，仍未见汞排出的进展。ATC和TT没有显示出任何影响。因此，在体外实验中，只有新合成的硫代巯基化合物中的TC对MM代谢有影响，而在体内实验中，TC也没有表现出预期的作用。为此，一个原因是药物在化学上不稳定，因此有必要在硫基物质的-S-S-H自由基中引入烷基末端而不是H末端。这方面的研究有待于今后继续深入。

Heavy metals taken into the tissues are transported among organs and are excreated out of the body sooner or later. In our previous studies, it was found that thiosulfydryl substances would play an important role in decreasing toxicity of heavy metals and eliminating metal concerned from the body. Thiocysteamine (TC), S-acetyl thiocysteamine (ATC) and thiotaurine (TT) were newly synthesized to investigate their detoxication effects on Methylmercury (MM) or Cd metabolism in tissues and urine.1. In vitro experiments; TC could libelate 40 to 90% of MM from the tissues pre-treated with MM, and MM added was also released from the tissues pre-incubated with TC. However, in the later experiment, the releasing effect diminished after pre-incubation for 100 min. As for Cd, observing Cd concrntration ratio of supernatant to residue and Cd contents in protein fractions in the liver preloaded with Cd, any changes were not found.2. In vivo experiments; The drugs were administered under the different conditions to mice pretreated with MM. The contents of mercury slightly increased in urine and decreased in kidney after the administration of TC alone, but no progression of mercury elimination was observed even in TC administration mixed wiyh either glutathione, cysteamine or Intrafat. ATC and TT did not reveal any effects. The significant effects on Cd movement in tissues were not recognized in case of the administration of TC to mice pretreated with Cd.Thus, only TC in thiosulfydryl substances newly synthesized manifested the effect on MM metabolism in vitro experiments, but even TC did not have the intended effect in vivo experiments. For this reason, one cause is that the drugs were chemically unstable, so it is necessary to introduce alkyl terminal instead of H-terminal in -S-S-H radical of thiosulfydryl substance. The further study should be continued in the future.