Effects of several dithiocarbamates on tissue distribution and excretion of inorganic mercury in rats

The effects of various chelating agents, sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-methylbenzyl-D-glucamine dithiocarbamate (MBGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), and N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD), which were newly synthesized, and sodium N-methyl-D-glucamine dithiocarbamate (MGD), on the distribution and excretion of inorganic mercury were compared in rats exposed to HgCl2. Rats were injected i.p. with 203HgCl2 (300 micrograms of Hg and 74 kBq of 203Hg/kg) and 30 min or 24 h later, they were injected with a dithiocarbamate (1200 mumol/kg). At 30 min after mercury administration, BGD and MBGD significantly enhanced the biliary excretion of mercury, while CBGD, MGD, and HBGD enhanced the urinary excretion of mercury to a small extent. At 24 h after mercury injection, BGD was the most effective on the biliary excretion of the metal, while MGD and HBGD significantly enhanced the urinary excretion of the metal. All of these dithiocarbamates were effective in mobilizing mercury from the kidney at 30 min after mercury treatment. At 24 h after mercury treatment, HBGD and BGD effectively depressed mercury content in the kidney. These results show that the injection of BGD and HBGD at both 30 min and 24 h after mercury treatment can much more effectively mobilize mercury from the kidney without redistribution of mercury to other tissues, such as brain, heart, and lung, when compared with injection of other chelating agents. The pattern of mobilization and excretion of mercury following treatment with each chelating agent was related to the organic/aqueous partition coefficient of each dithiocarbamate-mercury complex.     

Effect of N-benzyl-D-glucamine dithiocarbamate on renal toxicity of inorganic mercury in rats

The effect of N-benzyl-D-glucamine dithiocarbamate (BGD) on the renal toxicity of inorganic mercury in rats was studied. Rats were injected i.v. with saline or HgCl2 (300 micrograms Hg/kg) and 30 min later they were injected i.p. with saline or BGD (2778 mumol/kg, a quarter of an LD50). Urinary excretion of gamma-glutamyl-transpeptidase (gamma-GTP), which is a brush border enzyme, in rats after mercury treatment significantly increased compared to that of the control in the 12-24 h urine specimen and reached a maximum value within 24 h after the treatment. Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), which is a lysosomal enzyme, also significantly increased after mercury treatment compared to that of the control in the 12-24 h urine specimen and reached a maximum value within 48 h after the treatment. A change in urinary aspartate aminotransferase (AST) activity after mercury treatment followed a pattern similar to that observed with the urinary NAG. BGD treatment did not increase the urinary excretions of gamma-GTP, NAG, and AST. The uptake of p-aminohippuric acid (PAH) by renal cortical slices significantly decreased 24 h after mercury treatment. BGD injection after mercury treatment did not decrease the uptake of PAH by cortical slices. In addition, the microscopic examination of renal tissue from mercury-treated rats revealed necrosis of the proximal tubular cells. However, a photomicrograph of rat renal cortex after BGD treatment showed little abnormality. These results indicated that the mercury-induced renal damage was protected by the injection of BGD 30 min after mercury treatment.     

Protective effect of N-benzyl-D-glucamine dithiocarbamate against cis-diamminedichloroplatinum-induced toxicity in gastrointestinal tract and bone marrow in rats

The protective effect of N-benzyl-D-glucamine dithiocarbamate (BGD) against gastrointestinal and bone marrow toxicities produced by cis-diamminedichloroplatinum (DDP) injection in rats was studied. Rats were injected i.p. with BGD (2 mmol/kg) immediately after i.v. injection of DDP (20 mumol/kg). A scanning electron micrograph of the jejunum after DDP treatment showed damage in the villi, and that BGD protected the DDP-induced jejunal damage. BGD treatment also had a protective effect against DDP-induced diarrhea. BGD significantly reversed the reduction in maltase and sucrase activities of jejunal mucosa of rats treated with DDP. Platinum (Pt) concentrations in the gastrointestine as well as in the kidney and liver after DDP injection decreased following BGD treatment. The reduction of leukocytes following DDP injection returned to control values after BGD treatment. Biliary and urinary excretions of Pt after DDP injection was remarkably increased by BGD treatment. The results of this study indicated that the injection of BGD to rats treated with DDP can effectively remove Pt from the body through biliary and urinary excretions, resulting in protection of the gastrointestinal and bone marrow toxicities induced by DDP treatment.     

Application of a poly(dithiocarbamate) resin with macroreticular support to the determination of trace amounts of cadmium and lead in non-saline waters.

The chelating poly(dithiocarbamate) resin with macroreticular support is shown to be effective for the preconcentration of cadmium and lead from non-saline waters. The retained ions can be eluted efficiently in 5 ml of 8 mol dm-3 nitric acid from 1-20 cm columns of resin. Poly(dithiocarbamate) resin is used for preconcentration in the determination of cadmium and lead by flame atomic absorption spectrometry. The common ions present in non-saline waters do not interfere. The sensitivity was 0.10 micrograms l-1 of Cd and 0.73 micrograms l-1 of Pb. The detection limits were 0.03 and 0.34 micrograms l-1 for Cd and Pb, respectively. The cadmium and lead concentration rages, determined in mineral and tap waters, were between 0.1 and 0.8 micrograms l-1 and between 0.7 and 16.9 micrograms l-1, respectively.     

螯合剂与牛血清白蛋白竞争镉作用的研究

研究了十一种螯合剂使结合在牛血清白蛋白(BSA)上的镉活动化的能力。由凝胶色谱法测得的F值将螯合剂活动镉的能力排成以下顺序:DTP>EDTA>EGTA>NTA>TRIEN>;PEN>CYS>HIS>SA氨羧络合剂型配体能有效地与BSA竞争,而且它们的lgF与lgK_CdL间有一线性关系。     

Determination of 0.1 to 1000 μ g/ml cadmium in a hydrometallurgical zinc refining process stream by a flow injection technique with computer controlled injection method

A computer-controlled flow injection system was developed for the determination of cadmium in a hydrometallurgical zinc refining process stream. An anion-exchange method in acidic potassium iodide medium was used for the on-line separation of cadmium from the matrix zinc. 1-(4-Nitrophenyl)-3-(4-phenylazophenyl)triazene (Cadion) was used as the chromogenic reagent for the spectrophotometric detection of cadmium. In order to expand the dynamic range of the flow injection - spectrophotometry, a computer-aided time-based variable-volume injection method has been employed for the introduction of the sample into the flow injection system. Samples ranging from 0.56 to 350 microl can be delivered by controlling the time period of the sample introduction valve and the flow rate of the carrier solution. The system permits a throughput of 5 samples per hour. The reproducibility has been proven to be satisfactory with a relative standard deviation of less than 6.2% (sample injected: 0.56 microl of 850 microg Cd/ml; n=100) and 5.0% (350 microl of 0.14 microg Cd/ml; n=5). The determination limit was 20 microg Cd/ml with 0.56 microl sample injection and 0.05 microg Cd/ml with 350 microl sample injection (the absolute amount of cadmium injected into the system was 11 ng and 17.5 ng, respectively).     

Correlation between gastrointestinal absorption and uptake of radioisotopes by the critical organs

This study was undertaken to investigate the correlation between gastrointestinal absorption of radioisotopes and uptake by the critical organ during the same period using 85Sr, 109Cd, 131I and 203Hg as radioisotopes. When the distribution of 85Sr, 109Cd, 131I and 203Hg in mice were investigated by means of the whole body autoradiography, these critical organs were determined as follows; 85Sr: bone, 109Cd: liver, 131I: thyroid gland and 230Hg: kidney. When the correlation between the injected dose and the uptake dose by the critical organ of 85Sr, 109Cd, 131I and 203Hg were investigated, uptake dose the critical organ expressed as cpm per gram of organ was in direct proportion to the injected dose and that expressed as % of the injected dose per gram of organ was held constand in either case. When the coefficient of correlation between gastrointestinal absorption and uptake by the critical organ of 85Sr, 109Cd, 131I and 203Hg were calculated, a positive correlation was revealed in either case. It is concluded from the results obtained that in vivo or in situ method, gastrointestinal absorption of radioisotopes received a support from uptake by the critical organ during the same period.     

Preconcentration by dithiocarbamate extraction for determination of trace elements in natural waters by inductively-coupled plasma atomic emission spectrometry

Preconcentration by dithiocarbamate extraction into 2-ethylhexyl acetate for simultaneous determination of trace elements in natural water is described. After 250-fold concentration, the organic phase is used directly for inductively-coupled plasma atomic emission spectrometry. Thirteen elements (As, Se, Mo, Zn, Cd, Ni, Co, Sn, Fe, Cr(VI), Pb, V and Cu) are simultaneously concentrated at pH 4.3 with the combination of ammonium tetramethylenedithiocarbamate and dibenzylammonium dibenzyldithiocarbamate and are determined in the extract; Mn and Cr(III) are also determined after preconcentration at pH 6.9 with the same chelating agents. Lake waters are analyzed by this method.     

Musa sp. Leaves Extract Ameliorates the Hepato-Renal Toxicities Induced by Cadmium in Mice

Heavy metals intoxication causes several health problems that necessitate finding new protective and therapeutic approaches. This study aimed to evaluate the impact of Musa sp. leaves extract (MLE) on hepato-renal toxicities induced by cadmium (Cd) in male mice. The phytochemical screening, metal chelating activity (MCA), and the median lethal dose (LD₅₀) of MLE were determined. Fifty CD-1 male mice were used and intraperitoneally (i.p.) injected with MLE (1000 to 5000 mg/kg b.wt) for MLE LD₅₀ determination. Another 50 mice were used for evaluating the effect of MLE on Cd toxicity. Blood samples were collected for hematological, liver, and kidney functions assessments. Liver tissue homogenates were used for determination of oxidant/antioxidant parameters. Liver and kidney tissues were harvested for histopathological and molecular investigations. MLE showed potent in vitro antioxidant activities. The MCA and LD₅₀ of the MLE were 75 µg/mL and 3000 mg/kg b.wt, respectively. MLE showed beneficial therapeutic activity against hepato-renal toxicities in Cd-intoxicated mice, evidenced by improving the hematological, biochemical, histopathological, and molecular alterations.     

STUDIES ON THE COMPETITION FOR CADMIUM ION BETWEEN CHELATING AGENTS AND BOVINE SERUM ALBUMIN

Eleven chelating agents were studied for their capabilities to mobilize the cadmium bound tp bovine serum albumin(BSA).The parameter F,which is defined as the ratio between the percentages of cadmium bound to BSA in the presence and absence of chelating agents,can be used as the criterion to evaluate the mobilizing capability of chelating agent.The F values determined experimentally lead to a mobilizing capability order:DTPA>EDTA>EGTA>NTA>TR1EN>PEN>CYS>HIS>SAThe polyaminopolycarboxylate type chelators mobilize cadmium effectively.A linear relationship was found between 1gF and lg k'CdL (conditional stability constant of the cadmium chelate).     

Flow injection wetting-film extraction system for flame atomic absorption spectrometric determination of cadmium in environmental waters

A newly simple flow injection wetting-film extraction system coupled to flame atomic absorption spectrometry (FAAS) has been developed for trace amount of cadmium determination. The sample was mixed on-line with sodium diethyl dithiocarbamate and the produced non-charged Cd(II)-diethyl dithiocarbamate (DDTC) chelate complex was extracted on the thin film of diisobutyl ketone (DIBK) on the inner wall of the PTFE extraction coil. The wetting-film with the extracted analyte was then eluted by a segment of the cover solvent, and transported directly to the FAAS for evaluation. All the important chemical and flow parameters were optimized. Under the optimized conditions an enhancement factor of 35, a sample frequency of 22 h⁻¹ and a detection limit of c_L = 0.7 μg l⁻¹ Cd(II) were obtained for 60 s preconcentration time. The calibration curve was linear over the concentration range 1.5-45.0 μg l⁻¹ Cd(II) and the relative standard deviation, R.S.D. (n = 10) was 3.9%, at 10.0 μg l⁻¹ concentration level. The developed method was successfully applied to cadmium determination in a variety of environmental water samples as well as waste-water sample.     

急性镉中毒大鼠致死时重要器官镉的分布

分别通过静脉和呼吸道急性镉染毒，探讨了急性镉中毒大鼠致死时，血液，心、肝、肾、脑、肺的镉分布。８０只Ｗｉｓｔａｒ大鼠分为对照组和染毒组，氯化镉进行急性染毒，在心肌收缩功能降低为染毒前的５０％及心跳停止时，取器官标本，用原子吸收分光光度计测定镉含量。实验结果提示，急性镉中毒时，血液、心脏的镉含量早期升高缓慢，后期升高较快，肝脏镉含量呈线性快速升高；而肾脏镉含量经呼吸道染毒时与肝脏类似，经静脉染毒时，     

Stable and lipophilic technetium-99m dithiosemicarbazone complexes with 5-6-5 membered chelate ring structure

Modification of the chelate ring structure of technetium-99m (99mTc) dithiosemicarbazone (DTS) chelate was carried out in pursuit of a more stable and lipophilic compound. A new DTS chelating molecule, pentane-2,4-dione bis(N-methylthiosemicarbazone) (PETS), with a 5-6-5 membered chelate ring structure, was synthesized and labeled with 99mTc, PETS generated two 99mTc compounds as major products. Both had much higher stability and lipophilicity than a 5-5-5 membered 99mTc DTS compound, as well as great stability in plasma. Both 99mTc-PETS compounds were rapidly extracted by the brain and heart when injected into mice. Thus, the modified chelate ring structure afforded a preferable characteristics to DTS chelate as for the chelating site for technetium radiopharmaceuticals.     

The preparation and characterization of mono- and bis-chelated cadmium(II) complexes of the di-2-pyridylketone Schiff base of S-methyldithiocarbazate (Hdpksme) and the X-ray crystal structure of the [Cd(dpksme)2] · 0.5 MeOH complex

New cadmium(II) complexes of empirical formulae, [Cd(dpksme)X] (dpksme = anionic form of the Schiff base; X = NCS^–, Cl^–, I^–) and [Cd(dpksme)₂] · 0.5MeOH, respectively have been prepared and characterized. The mono-ligated cadmium(II) complexes, [Cd(dpksme)X] are four-coordinate and tetrahedral but the bis-ligand complex, [Cd(dpksme)₂] · 0.5MeOH is six-coordinate and octahedral. The crystal and molecular structure of [Cd(dpksme)₂] · 0.5MeOH has been determined by X-ray diffraction. The complex has a distorted mer-octahedral structure in which the ligands are coordinated as uninegatively charged tridentate chelating agents via the pyridine nitrogen atoms, the azomethine nitrogen atoms and the thiolate sulfur atoms. The distortion from regular octahedral geometry is ascribed to the restricted bite angles of the ligands. The Schiff base and its cadmium(II) complexes exhibit mild antibacterial activities against Shigella dysenteriae, Bacillus cereus, Staphylococcus aureus and Escherichia coli. They are also mildly fungitoxic against the phytopathogenic fungi, Alternaria alternata and Macrophomina phaseolina.     

Synthesis and characterization of group 12 complexes of N,N-methyl phenyl-N,N-butyl phenyl dithiocarbamate

Zn(II), Cd(II), and Hg(II) complexes of N-methyl-N-phenyl dithiocarbamate (L¹) and N-butyl-N-phenyl dithiocarbamate (L²) formulated as ML¹L² have been synthesized and characterized by elemental analysis, FT–IR, ¹H- and ¹³C-NMR spectroscopic techniques. Single-crystal X-ray structures of the Zn(II) and Hg(II) complexes are also reported. X-ray crystal structures revealed that in the zinc(II) complex, the dithiocarbamate is chelating and bridging, forming eight-member rings, while the Hg complex is monomeric with bidentate dithiocarbamate. In both complexes, the metals are in distorted tetrahedral geometry and the methyl and butyl groups of the dithiocarbamates exhibit compositional disorder between two positions.     

Determination of zinc and cadmium in small amounts of biological tissues by microwave- assisted digestion and flow injection atomic absorption spectrometry

A microwave oven/flow injection/amotic absorption spectrometric system that permits the determination of zinc and cadmium in small samples of human kidney and liver tissue (ca. 1 g) is described. Digested samples are pumped to a closed flow circuit from which aliquots (20 λ for Zn and 100 μl for Cd) are injected for atomic absorption spectrometry. Precision (ca. 2–6% RSD) and recovery (97–103% for Zn and 96–98% for Cd) are good. Accuracy is confirmed by standard additions and use of standard reference materials. Data obtained for male and female human liver and kidney samples are presented.     

工程化蛋白质纳米孔实时监测镉离子与谷胱甘肽的单分子反应

本研究利用合成的全-6-季铵基-β-环糊精(Per-6-quaternary ammonium-β-cyclodextrin,p-QABCD)装备基因工程化的α-溶血素(α-Hemolysin,αHL)蛋白质纳米孔(M113R)7,构建全新的单分子纳米孔反应器,在单分子水平实现对谷胱甘肽(GSH)和镉离子(Cd2+)的络合反应的实时原位监测,并辨认络合反应的不同路径、反应中间产物和最终产物.结果表明,溶液的pH值显著影响GSH与Cd2+络合产物的络合比例.pH=7.4时,GSH与Cd2+络合反应的最终产物为Cd(GSH)2;pH=9.0时,最终产物为Cd(GSH)2和Cd2(GSH)2.其中,Cd2(GSH)2的形成遵循两种路径:(1)一个Cd2+首先结合两个GSH分子的巯基形成Cd(GSH)2,然后,第二个Cd2+结合去质子化的氨基形成Cd2(GSH)2;(2)两个Cd2+分别结合同一个GSH分子的巯基和去质子化的氨基形成Cd2(GSH)1,然后,第二个GSH分子的巯基和去质子化的氨基结合Cd2(GSH)1的Cd2+形成Cd2(GSH)2.本研究实现了在单分子水平无标记和无化学修饰研究金属离子和生物小分子的反应,对理解细胞内重金属的解毒机理和拓展纳米孔单分子技术的研究领域具有重要意义.     

Crystallographic report: Bis[bis(N,N‐dibenzyldithiocarbamato)cadmium(II)]

The centrosymmetric structure of {Cd[S₂CN(CH₂Ph)₂]₂}₂ features both bridging and chelating dithiocarbamate ligands so that a square pyramidal S₅ coordination geometry results. Copyright © 2004 John Wiley & Sons, Ltd.     

Determination of traces of cadmium in natural water samples by flow injection on-line preconcentration-graphite furnace atomic absorption spectrometry.

A flow injection on-line preconcentration-graphite furnace atomic absorption spectrometric method was developed for the determination of traces of cadmium in natural water samples. Cadmium in samples was adsorbed on an iminodiacetate-type chelating resin, Muromac A-1 microcolumn (3 mm i.d. and 10 mm long), and then eluted with 2 mol l-1 HNO3. The eluate was introduced into the injection tip of an autosampler. The eluate zone with the highest analyte concentration was injected into the graphite furnace by cooperation of a peristaltic pump and a syringe pump of the autosampler, which were controlled by a programmable controller. The present system was successfully applied to the determination of cadmium in natural water samples. A detection limit of 0.2 ng l-1 was obtained with 12 ml sample loading. The recoveries were 99 and 108% for tap water (4 ml loading) and underground water (12 ml loading), respectively. Analytical results obtained for a river water reference material (JAC-0031, Japan Society for Analytical Chemistry) were close to the reference value.     

治疗冠心病中药的微量元素测定

对治疗冠心病中药丹参、降香、红花、茯苓及复方丹参注射液中铜、锌、铅、镉的含量 进行了测定。结果表明,其中必需微量元素铜、锌含量均比有害元素铅、镉的含量要高出1－2个数量级,其铜／锌比值与正常人血清铜／锌比值能较好地吻合,镉／锌比值较低。