Bláha K, Nerudová J, Jehlicová H, Cikrt M, Jones M M, Singh P K
Center for Industrial Hygiene and Occupational Disease, National Institute of Public Health, Prague, Czech Republic.
J Toxicol Environ Health. 1995 Jan;44(1):87-100. doi: 10.1080/15287399509531945.
Female Wistar rats with chronic cadmium intoxication (oral exposure to low dosages of CdCl2 in drinking water over a period of 90 d) were used to examine the in vivo ability of a newly developed chelator, sodium N-(4-methylbenzyl)-4-O-(beta-D-galactopyranosyl)-D-glucamine-N- carbodithioate (MeBLDTC), singly and in combination with sodium 4-carboxy-amidopiperidine-N-carbodithioate (INADTC) as agents to induce the biliary and urinary excretion of cadmium. The combined administration of the two dithiocarbamates, which differ greatly in molecular weight and structural features, led to a synergistic increase in the biliary excretion of cadmium and an enhanced reduction of renal cadmium levels. The use of such a coadministration produced an increase in the biliary excretion of cadmium that was more than double that expected if the compounds acted in an additive fashion. Such mixed-chelation therapy has potential utility in the treatment of human chronic cadmium intoxication. The hepatocytes isolated from chronically Cd-intoxicated rats were used as an in vitro screening model system for the new chelator. The plasma membrane integrity study with MeBLDTC at 0.48 mmol/20 ml of hepatocyte incubate using the trypan blue exclusion test and lactate dehydrogenase (LDH) leakage test revealed no differences in the cell viability with or without chelator. The cellular metabolic competence measured as the rate of urea synthesis also did not show any marked deviation from that of controls when incubated with MeBLDTC at three different concentrations. In the hepatocyte cultures, MeBLDTC induced a significant removal of cadmium from the hepatocytes at concentrations as low as 0.04 mmol/20 ml.
选用慢性镉中毒的雌性Wistar大鼠（通过在90天内饮用含低剂量CdCl₂的水进行口服暴露），以研究一种新开发的螯合剂N-(4-甲基苄基)-4-O-(β-D-吡喃半乳糖基)-D-葡糖胺-N-碳二硫代酸钠（MeBLDTC）单独以及与4-羧基-氨基哌啶-N-碳二硫代酸钠（INADTC）联合作为诱导镉经胆汁和尿液排泄的药物的体内能力。这两种二硫代氨基甲酸盐的分子量和结构特征差异很大，联合给药导致镉的胆汁排泄协同增加，肾脏镉水平进一步降低。这种联合给药使镉的胆汁排泄增加，若化合物以相加方式起作用，增加量应超过预期的两倍。这种混合螯合疗法在治疗人类慢性镉中毒方面具有潜在应用价值。从慢性镉中毒大鼠分离的肝细胞用作新螯合剂的体外筛选模型系统。使用台盼蓝排斥试验和乳酸脱氢酶（LDH）泄漏试验，在0.48 mmol/20 ml肝细胞培养液中对MeBLDTC进行质膜完整性研究，结果显示添加或不添加螯合剂时细胞活力无差异。以尿素合成速率衡量的细胞代谢能力，在与三种不同浓度的MeBLDTC孵育时，也未显示出与对照组有任何明显偏差。在肝细胞培养中，MeBLDTC在低至0.04 mmol/20 ml的浓度下就能显著诱导肝细胞中镉的去除。
