Jasim S, Tjälve H
Toxicology. 1984 Sep 28;32(4):297-313. doi: 10.1016/0300-483x(84)90082-9.
Oral administration of 63Ni2+ together with thiuram sulphides (tetramethylthiuram disulphide, tetraethylthiuram disulphide, tetrabutylthiuram disulphide, dipentamethylenethiuram monosulphide or dipentamethylenethiuram tetrasulphide) or sodium diethyldithiocarbamate resulted in highly increased levels of 63Ni2+ in several tissues of mice in comparison with animals given 63Ni2+ alone. Administration of these substances to pregnant animals induced increased levels of 63Ni2+ in the fetuses. The uptake of 63Ni2+ in the brains of both adults and fetuses was usually very markedly enhanced by these compounds--dipentamethylenethiuram monosulphide and tetraethylthiuram disulphide being the most efficient compounds in this respect. Determination of the chloroform/water partition coefficients for nickel in the presence of thiuram sulphides or sodium diethyldithiocarbamate showed that these compounds are able to form lipophilic complexes with the metal. A facilitated penetration through the cellular membranes of the lipophilic complexes between nickel and these substances can explain the effects on the fate of the nickel. However, the partition coefficient for nickel in presence of sodium diethyldithiocarbamate was much higher than for the thiuram sulphides, but in spite of that, the effect of sodium diethyldithiocarbamate on the disposition of 63Ni2+ in the mice was not more marked than for most of the thiuram sulphides. It has been shown that tetraethylthiuram disulphide undergoes a reductive fission in the gut to diethyldithiocarbamate, which is considered to be the active form of tetraethylthiuram disulphide. The marked effects on the disposition of the 63Ni2+ induced by the other thiuram sulphides examined in the present study suggest that a similar fission to chelating thiocarbamates will take place. However, the formation of lipophilic complexes with the original thiuram sulphides may contribute to the effects on the disposition of the 63Ni2+.
与二硫化四甲基秋兰姆、二硫化四乙基秋兰姆、二硫化四丁基秋兰姆、一硫化二五亚甲基秋兰姆或四硫化二五亚甲基秋兰姆等秋兰姆硫化物或二乙基二硫代氨基甲酸钠一起口服63Ni2+，与单独给予63Ni2+的动物相比，小鼠多个组织中的63Ni2+水平显著升高。给怀孕动物施用这些物质会导致胎儿体内63Ni2+水平升高。这些化合物（一硫化二五亚甲基秋兰姆和二硫化四乙基秋兰姆在这方面最为有效）通常会非常显著地增强成年动物和胎儿大脑对63Ni2+的摄取。在秋兰姆硫化物或二乙基二硫代氨基甲酸钠存在下测定镍的氯仿/水分配系数表明，这些化合物能够与金属形成亲脂性络合物。镍与这些物质之间的亲脂性络合物促进了穿过细胞膜的渗透，这可以解释对镍命运的影响。然而，在二乙基二硫代氨基甲酸钠存在下镍的分配系数远高于秋兰姆硫化物，但尽管如此，二乙基二硫代氨基甲酸钠对小鼠体内63Ni2+分布的影响并不比大多数秋兰姆硫化物更显著。已经表明，二硫化四乙基秋兰姆在肠道中会发生还原裂变生成二乙基二硫代氨基甲酸钠，后者被认为是二硫化四乙基秋兰姆的活性形式。本研究中检测的其他秋兰姆硫化物对63Ni2+分布的显著影响表明，会发生类似的裂变生成螯合硫代氨基甲酸盐。然而，与原始秋兰姆硫化物形成亲脂性络合物可能有助于对63Ni2+分布产生影响。
