Effects of Thiosulfydryl Substances on the Metabolism of Heavy Metals

硫代硫基物质对重金属代谢的影响

• 批准号: 60480190
• 负责人: SUMINO Kimiaki
• 金额: $ 0.32万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60480190/
• 关键词: Thiosulfydryl; Thiocysteamine; Methyl Mercury; Cadmium; Detoxication; 重金属代謝

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.

进入组织的重金属会在器官之间运输，并迟早被排出体外。我们在前期的研究中发现，硫代硫基物质在降低重金属毒性、消除体内相关金属方面发挥着重要作用。新合成了硫代半胱胺(TC)、S-乙酰硫代半胱胺(ATC)和硫牛磺酸(TT)，研究它们对组织和尿液中甲基汞(MM)或镉代谢的解毒作用。1．体外实验； TC可以从用MM预处理的组织中释放40%至90%的MM，并且添加的MM也可以从用TC预孵育的组织中释放。然而，在后来的实验中，预孵育100分钟后释放效果减弱。对于Cd，观察预载Cd的肝脏中上清液与残渣的Cd浓度比以及蛋白质组分中的Cd含量，未发现任何变化。 2．体内实验；在不同条件下对经过 MM 预处理的小鼠施用药物。单独施用TC后，尿中汞含量略有增加，肾脏中汞含量略有减少，但即使TC与谷胱甘肽、半胱胺或Intrafat混合施用，也没有观察到汞消除的进展。 ATC 和 TT 没有显示任何影响。在给经过Cd预处理的小鼠施用TC的情况下，没有发现对组织中Cd运动的显着影响。因此，在体外实验中，只有新合成的硫代硫基物质中的TC表现出对MM代谢的影响，但即使是TC在体内实验中也没有达到预期的效果。原因之一是药物化学性质不稳定，因此需要在硫代硫基物质的-S-S-H基团中引入烷基端而不是H端。今后应继续进一步研究。

项目成果

Mio T., Yamamoto R. and Sumino K.: "Elimination of Metylmercury by Hydrodisulfide. - Excretion Rate and Chemical Form -" Jap. J. Hyg.42. in press (1987)

Mio T.、Yamamoto R. 和 Sumino K.：“通过氢二硫化物消除甲基汞。-排泄率和化学形式 -”Jap。

Sumino K.;Mio T.: The 【III】rd COMTOX on Bio-and Toxicokinetics of Metals. 125 (1986)

Sumino K.；Mio T.：第 [III]rd COMTOX 关于金属的生物和毒代动力学 125 (1986)

三尾隆弥,住野公昭: 日本衛生学会雑誌. 40. 298-298 (1985)

Takaya Mio，Kimiaki Sumino：日本卫生学会杂志 40. 298-298 (1985)。

三尾隆弥,山本良二,住野公昭: 日本衛生学会雑誌. 42. (1987)

Takaya Mio、Ryoji Yamamoto、Kimiaki Sumino：日本卫生学会杂志 42。（1987 年）

Mio T. and Sumino K.: "Elimination of Metylmercury by Hydrodisulfide. (2) - Research in Animals -" Jap. J. Hyg.40. 298 (1985)

Mio T. 和 Sumino K.：“通过氢二硫化物消除甲基汞。(2) - 动物研究 -”日本。