COMPARATIVE EFFECTS OF 10 DITHIOCARBAMATE AND THIURAM COMPOUNDS ON TISSUE DISTRIBUTION AND EXCRETION OF LEAD IN RATS
COMPARATIVE EFFECTS OF 10 DITHIOCARBAMATE AND THIURAM COMPOUNDS ON TISSUE DISTRIBUTION AND EXCRETION OF LEAD IN RATS
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DOI：
10.1016/s0013-9351(87)80088-9
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发表时间：
1987-10-01
影响因子：
8.3
通讯作者：
OSKARSSON, A
中科院分区：
文献类型：
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作者：
OSKARSSON, A
已知用铅和双硫仑联合治疗大鼠会导致大脑中铅含量增加并增强铅的神经毒性。比较了包括双硫仑在内的 10 种二硫代氨基甲酸盐和秋兰姆化合物对大鼠静脉注射微量铅加 203Pb 的组织分布的影响效果。测试的化合物是二乙基二硫代氨基甲酸钠（DEDTC）、二甲基二硫代氨基甲酸钠（DMDTC）、二硫化四乙基秋兰姆（双硫仑）、亚乙基双二硫代氨基甲酸锌和锰的络合物（代森锰锌）、亚乙基双二硫代氨基甲酸锰（代森锰）、单甲基二硫代氨基甲酸钠（速百胜）、丙烯双二硫代氨基甲酸锌（丙代森锌）、二硫化四甲基秋兰姆（福美双）、亚乙基双二硫代氨基甲酸锌（代森锌）和二甲基二硫代氨基甲酸锌（齐拉姆）。口服和皮下注射 DEDTC、DMDTC、双硫仑、威丹、福美双和吉美联后，发现对铅的组织分布有显着影响。与仅接受铅的对照大鼠相比，口服给药后，脑、肝、肺和脾中铅的吸收增加，而股骨中铅的吸收减少。福美双是增强大脑铅吸收最有效的化合物，在 72 小时存活时导致 203Pb 浓度增加 100 倍。皮下注射后，威百胺引起脑内 203Pb 浓度的最高增加。铅的粪便排泄是铅的主要排泄途径，在口服双硫仑、齐美仑和福美双后，48小时时对照大鼠的排泄量减少至约20%。除代森锌治疗组外，所有治疗组中铅的尿排泄量均显着减少。对组织分布和排泄的影响可以通过体内铅与这些化合物或其代谢物之间形成的亲脂性复合物来解释，该复合物促进铅通过细胞膜和血脑屏障的转运。代森锌、代森锌、丙森锌和代森锰锌不会对铅的组织分布产生类似的影响。这项研究的结果表明，铅与 DEDTC、DMDTC、双硫仑、威丹、福美双和福美双之间可能发生相互作用，导致大脑中铅水平增加，并可能增强铅的神经毒性作用。
Combined treatment of rats with lead and disulfiram is known to cause increased levels of lead in brain and potentiation of the neurotoxicity of lead. Ten dithiocarbamate and thiuram compounds, including disulfiram, were compared for their efficacies in influencing tissue distribution of trace dose of intravenously injected lead plus 203Pb in rats. The tested compounds were sodium diethyldithiocarbamate (DEDTC), sodium dimethyldithiocarbamate (DMDTC), tetraethylthiuram disulfide (disulfiram), a complex of zinc and manganese ethylenebisdithiocarbamate (mancozeb), manganese ethylenebisdithiocarbamate (maneb), sodium monomethyldithiocarbamate (metham), zinc propylene bisdithiocarbamate (propineb), tetramethylthiuram disulfide (thiram), zinc ethylenebisdithiocarbamate (zineb), and zinc dimethyldithiocarbamate (ziram). Pronounced effects on tissue distribution of lead were seen after peroral and subcutaneous administration of DEDTC, DMDTC, disulfiram, metham, thiram, and ziram. After peroral administration there was an increased uptake of lead in brain, liver, lung and spleen and a decreased uptake in femur compared to control rats receiving only lead. Thiram was the most effective compound in enhancing lead uptake in brain, causing a 100-fold increase in 203Pb concentration at 72 hr survival. After subcutaneous administration, metham caused the highest increase in brain concentration of 203Pb. Fecal excretion of lead, which is the main excretory pathway, was decreased after peroral administration of disulfiram, ziram, and thiram to about 20% of the excretion in control rats at 48 hr. Urinary excretion of lead was significantly decreased in all the treated groups except the group treated with zineb. The effects on tissue distribution and excretion can be explained by in vivo formation of lipophilic complexes between lead and these compounds or their metabolites facilitating the transport of lead through cell membranes and the blood-brain barrier. Zineb, maneb, propineb, and mancozeb did not cause similar effects on the tissue distribution of lead. The results of this study show that interactions can occur be between lead and DEDTC, DMDTC, disulfiram, metham, thiram, and ziram, resulting in increased levels of lead in brain and probably potentiation of the neurotoxic effects of lead.