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二硫醇和二硫代氨基甲酸盐螯合剂在降低大鼠体内钋-210潴留方面的相对有效性

Relative effectiveness of dithiol and dithiocarbamate chelating agents in reducing retention of polonium-210 in rats.

作者信息

Rencová J, Volf V, Jones M M, Singh P K

机构信息

National Institute of Public Health, Centre of Radiation Hygiene, Praha, Czechoslovakia.

出版信息

Int J Radiat Biol. 1993 Feb;63(2):223-32. doi: 10.1080/09553009314550291.

Abstract

Nine different sulphur-based chelators, including dithiols and dithiocarbamates, were examined for their ability to remove Po-210 from the rat. In general, treatments merely caused a redistribution of Po-210 in the body. Greatest reduction of Po-210 in blood was achieved by 2,3-dimercaptopropanol (BAL), sodium diethyldithiocarbamate (DDTC), and N-(2,3-dimercaptopropyl) phthalamidic acid (DMPA). Nearly all the compounds tested decreased Po-210 in the spleen and muscle. On the other hand, BAL and DDTC substantially increased the accumulation of Po-210 in the brain while DMPA, DMPS (sodium 2,3-dimercaptopropane-1-sulphonate) and DMSA (meso-2,3-dimercaptosuccinic acid) increased by several times the Po-210 in kidneys. A less pronounced increase of Po-210 was sometimes observed in liver (due to DDTC and DMPA) and in muscle (due to BAL and DDTC). Three of the dithiocarbamates (BGDTC, MeOBGDTC and BLDTC) did not increase accumulation of Po-210 in the brain and muscle but they reduced Po-210 in blood to a lesser degree than DDTC. A derivative of DMSA (Mi-ADMS) reduced Po-210 in blood, bone and muscle more than DMSA, but at the same time increased Po-210 in the kidney. When BAL or DDTC were combined with other agents there was a greater reduction in the whole-body burden of Po-210. Removal of Po-210 from the bone, spleen and kidneys by BAL was increased by repeated treatment. However, under similar experimental conditions the effect of a single injection of BAL on Po-210 in blood was less pronounced when the period of observation was prolonged. Total-body retention of Po-210 could not be reduced to less than 85% of the untreated controls by any of the chelators tested. In spite of this some of them (BAL, DMPS, DMSA, DMPA) could still have a useful role in reducing the toxicity of Po-210.

摘要

研究了九种不同的硫基螯合剂,包括二硫醇和二硫代氨基甲酸盐,考察它们从大鼠体内去除钋 - 210的能力。一般来说,这些处理仅仅导致钋 - 210在体内重新分布。2,3 - 二巯基丙醇(BAL)、二乙基二硫代氨基甲酸钠(DDTC)和N -(2,3 - 二巯基丙基)邻苯二甲酰胺酸(DMPA)使血液中钋 - 210的减少最为显著。几乎所有测试的化合物都能降低脾脏和肌肉中的钋 - 210含量。另一方面,BAL和DDTC显著增加了大脑中钋 - 210的蓄积,而DMPA、二巯基丙磺酸钠(DMPS)和二巯基丁二酸(DMSA)使肾脏中钋 - 210的含量增加了几倍。有时在肝脏(由于DDTC和DMPA)和肌肉(由于BAL和DDTC)中观察到钋 - 210有不太明显的增加。三种二硫代氨基甲酸盐(BGDTC、MeOBGDTC和BLDTC)不会增加大脑和肌肉中钋 - 210的蓄积,但它们使血液中钋 - 210减少的程度比DDTC小。二巯基丁二酸的一种衍生物(Mi - ADMS)比DMSA更能降低血液、骨骼和肌肉中的钋 - 210,但同时增加了肾脏中钋 - 210的含量。当BAL或DDTC与其他药物联合使用时,全身钋 - 210的负荷降低得更多。重复使用BAL可增加其从骨骼、脾脏和肾脏中去除钋 - 210的能力。然而,在类似的实验条件下,当观察期延长时,单次注射BAL对血液中钋 - 210的影响就不那么明显了。所测试的任何一种螯合剂都不能使钋 - 210的全身滞留量降低到未处理对照组的85%以下。尽管如此,它们中的一些(BAL、DMPS、DMSA、DMPA)在降低钋 - 210的毒性方面仍可能发挥有益作用。

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