Tjälve H, Borg-Neczak K
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
Sci Total Environ. 1994 Jun 6;148(2-3):217-42. doi: 10.1016/0048-9697(94)90399-9.
Dithiocarbamates, thiuram sulphides, xanthates, pyridinethiones and halogenated 8-hydroxyquinolines are groups of compounds which can form lipophilic complexes with Ni2+. These compounds are widely used as drugs and pesticides, and in industry. We have exposed rodents (mice, rats) and fish (brown trout) to substances belonging to these groups of compounds together with 63Ni2+ (as 63NiCl2) and then examined the uptake of the 63Ni2+ in the tissues of the animals. One dithiocarbamate--sodium diethyldithiocarbamate, which is used clinically in nickel carbonyl intoxications--was also examined with regard to effects on the tissue disposition of the metal in mice exposed to 63Ni(CO)4. The studies with 63Ni2+ showed that some of the complexing substances examined caused highly increased tissue levels of the metal in the animals. However, the enhancing effect varied with different complexing compounds. A facilitated penetration of the lipophilic 63Ni2+ complexes across the cellular membranes may underlie the increments in the tissue levels of the metal, but the effects on the disposition of the 63Ni2+ may vary depending on the lipophilicity and the stability of the complexes. In mice exposed to 63Ni(CO)4 by inhalation, sodium diethyldithiocarbamate decreased the levels of the metal in tissues such as the lung, brain and heart. These tissues are targets in nickel carbonyl intoxications and will attain high levels of the metal following inhalation of the compound. The nickel is present in nickel carbonyl as Ni0, but will be oxidized to Ni2+ in the tissues. The experiments presented here indicate that the diethyldithiocarbamate is able to reach and bind the intracellular Ni2+ in the critical target tissues and this property may underlie the ability of the compound to act as an antidote in nickel carbonyl intoxications. However, the ability of diethyldithiocarbamate to act as a nickel antidote may be limited to nickel carbonyl. Generally, the increased uptake of nickel induced by the compounds forming lipophilic complexes with the metal may imply risks of noxious combination effects.
二硫代氨基甲酸盐、秋兰姆硫化物、黄原酸盐、吡啶硫酮和卤代8-羟基喹啉是能够与Ni2+形成亲脂性络合物的几类化合物。这些化合物在药物、农药以及工业领域都有广泛应用。我们让啮齿动物（小鼠、大鼠）和鱼类（褐鳟）接触属于这些化合物类别的物质以及63Ni2+（以63NiCl2形式），然后检测动物组织中63Ni2+的摄取情况。还研究了一种二硫代氨基甲酸盐——二乙基二硫代氨基甲酸钠（临床上用于羰基镍中毒）对接触63Ni(CO)4的小鼠体内金属组织分布的影响。用63Ni2+进行的研究表明，所检测的一些络合物质会导致动物体内金属的组织水平大幅升高。然而，增强作用因不同的络合化合物而异。亲脂性63Ni2+络合物跨细胞膜的通透性增强可能是金属组织水平升高的原因，但对63Ni2+分布的影响可能因络合物的亲脂性和稳定性而异。在通过吸入接触63Ni(CO)4的小鼠中，二乙基二硫代氨基甲酸钠降低了肺、脑和心脏等组织中的金属水平。这些组织是羰基镍中毒的靶器官，吸入该化合物后会积累高水平的金属。羰基镍中的镍以Ni0形式存在，但在组织中会被氧化为Ni2+。此处呈现的实验表明，二乙基二硫代氨基甲酸盐能够到达并结合关键靶组织中的细胞内Ni2+，这一特性可能是该化合物在羰基镍中毒中起到解毒剂作用的基础。然而，二乙基二硫代氨基甲酸盐作为镍解毒剂的能力可能仅限于羰基镍。一般来说，与金属形成亲脂性络合物的化合物导致镍摄取增加可能意味着存在有害联合效应的风险。
