Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relative efficacy of thiol-containing mercurial scavengers was assayed by using cellular suspensions of erythrocytes or isolated hepatocytes. The blood cells incubated in a buffer (pH 7.4) containing 1 mM glucose (10% hematocrit) were exposed to 5 microM methyl mercuric chloride. In the absence of extracellular thiols the red blood cells took up more than 90% of methyl mercury from the surrounding medium during 5--10 min. This uptake was almost completely inhibited by dimercaptosuccinic acid (DMSA) (1 mM) and the same chelant could rapidly remove 80% of the mercury from 'pre-loaded' erythrocytes. Hepatocytes prepared according to the method of Seglen [11] in a suspension of 10(6) cells/ml in a buffer containing 5 mM glucose and 5 mg/ml of bovine serum albumin were also exposed to methyl mercuric chloride (4 microM). Almost 50% of the mercurial was taken up by the cells slowly during the incubation period of 240 min. DMSA (1 mM) almost completely blocked the methyl mercury binding by the hepatocytes. 2-Mercaptopropionylglycin (Thiola) or mercaptosuccinic acid (MSA) was almost as effective mercurial scavengers as DMSA in hepatocytes and in red blood cells. Diethyldithiocarbamate (DDC) and dimercaptopropanol (BAL) were considerably less effective than DMSA to inhibit the mercurial binding to hepatocytes. Experiments in vivo have shown that DMSA is a better mercurial chelator than Thiola or MSA, whereas DDC and BAL may both be considered to be inapplicable in methyl mercury poisonings. Our cellular assay provides preliminary information of the efficiency of chelating thiols and may serve as a useful first approximation when planning further experiments.
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PMID:Evaluation of methyl mercury chelating agents using red blood cells and isolated hepatocytes. 728 35

The chelating drugs BAL (2,3-dimercaptopropanol), EDTA (ethylenediaminetetraacetic acid), and penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), which are used for metal poisoning, are toxic and there is a real need for alternatives, especially for severe cases. A novel approach for treatment of heavy-metal poisoning is under investigation in our group. The approach utilizes the synthesis of chelating microspheres specific for the desired metallic compound. The microspheres are suggested for use in severe cases by means of hemoperfusion, as a first aid, and then by oral administration. As a model this approach was tried for mercury poisoning. Polymercaptal microspheres of 0.8 micrometer average size were synthesized. The microspheres have a high surface area, have a high affinity toward organic and inorganic mercury compounds, and can compete easily with albumin and cysteine in the ability to bind mercury compounds. These microspheres also were encapsulated with agarose--a blood compatible polymer--and were tried successfully for plasma perfusion (in 10 min, 40% of CH3HgCl and of HgCl2 were removed from 20 ppm of poisoned plasma).
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PMID:A novel approach for heavy metal poisoning treatment, a model. Mercury poisoning by means of chelating microspheres: hemoperfusion and oral administration. 732 90

The distribution and excretion of mercury were studied in mice and rats given a single injection of HgCl2 combined with chelation treatment. BAL-sulph (2,3-dimercaptopropane-1-sulphonate) given intravenously (500 mumol SH/kg) to mice 24 hrs after the mercury injection (2.0 mumol Hg/kg) reduced the kidney Hg-level significantly, while NAPA (N-acetyl-DL-penicillamine) and BAL (2,3-dimercaptopropanol) did not. Severe kidney damage with oliguria was observed in pregnant as well as in non-pregnant rats after injection of 5 mumol/kg of HgCl2. The gross pathological changes could be avoided with immediate treatment with BAL-sulph (500 mumol SH/kg), and such treatment protect against the oliguric reaction. Treatment delayed for 24 hrs reduced the renal Hg-levels significantly, but was ineffective in preventing the kidney damage. This indicates that irreversible changes might have occurred in kidneys cells at this time. The Hg-levels in the brain were either unchanged or lowered in animals given BAL-sulph treatment. BAL-sulph is supposed to act by chelation Hg++, particularly in the extracellular space. The complexes formed appears to be rapidly excreted by healthy kidneys. Mercury poisoning with severe renal damage is, however, associated with a block in urinary Hg-excretion. The poisoned animals responded on the BAL-sulph treatment with a substantial raise of faecal mercury excretion.
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PMID:The effect of immediate and delayed treatment with 2,3-dimercaptopropane-1-sulphonate on the distribution and toxicity of inorganic mercury in mice and in foetal and adult rats. 736 70

A comparison in mice has been made of the effectiveness of five chelating agents used clinically for acute mercuric chloride poisoning, or recommended for such use. The compounds examined were N-Acetyl-D,L-penicillamine (NAPA), D-penicillamine (DPA), 2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercaptopropanesulfonate (DMPS), and 2,3-dimercaptopropanol-1 (BAL). The test of effectiveness was their ability to reduce the mortality of acute mercuric chloride poisoning when administered 20 minutes after the mercury at chelate:mercury mole ratios of 10, 15, 20, and 30. All except BAL were found to be effective at the highest mole ratio tested, but N-Acetyl-D,L-penicillamine and sodium 2,3-dimercaptopropanesulfonate were significantly more effective than DMSA and BAL at mole ratios of 10:1. The relative effectiveness does not correlate with available data on stability constants. The toxicity of BAL itself becomes apparent at mole ratios of 20:1 and above.
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PMID:Comparison of standard chelating agents for acute mercuric chloride poisoning in mice. 736 52

Mercury binding to bile components and the correlation between the amount of mercury bound in the bile fraction 2 and the rate of mercury biliary excretion were studied in female rats exposed to intravenously injected HgCl2 after pretreatment with a series of 14 chemical agents. After pretreatment with the tested agent, 203Hg was detectable both in the bile fraction 1 and 2. Distribution pattern of 203Hg between the two fractions appeared to be linked with the chemical structure of the formed mercury complex. Pretreatment with these agents did not inhibit the formation of the bile fraction 3. By their influence on the 203Hg distribution between the bile fractions 1 and 2, the tested agents can be roughly divided into 3 groups: the content of 203Hg in the bile fraction 2 is about 10--20% and does not change significantly within the first 24 hours after 203 HgCl2 injection (cysteine, penicillamine, disodium ethylenediaminotetraacetate -- Na2EDTA, sodium diethyldithiocarbamate, sodium alanindithiocarbamate, acrylonitrile); the the 203Hg content in the bile fraction 2 increases (thiophenolacetate); the content of 203Hg in fraction 2 is initially several times higher than that in the bile fraction 1, but then decreases during the first 24 hours (2,3-dimercaptopropanol -- BAL, sodium 2,3-dimercaptopropanesulphonate, spironolactone, Thiomestron). The rate of mercury biliary excretion (Rb) was found to be closely correlated with the relative amount of mercury present in the bile fraction 2 (a2), if a2 > 30%, both in vivo (Rb = 1.077 a2 + 0.758) and invitro (Rb = 1.067 a2 + 0.519) experiments. Practically identical values of the constant accompanying a2 in the two equations seem to indicate that one of the decisive factors influencing the rate of mercury biliary excretion in rats is rather the mercury affinity for the bile fraction 2 components than the agent-induced mercury transport mechanisms. For a2 < 30% the correlation is non-linear and the excretion is rather inhibited than enhanced.
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PMID:Effect of some chelating agents on the biliary excretion of mercury. 2. Relationship between the excretion of mercury and its binding to bile fractions. 744 Sep 65

Wistar strain female rats were used to study the impact of 1-cysteine,D,L-penicillamine, EDTA, sodium N,N-diethyldithiocarbamate, BAL, Unitiou, Spironolactone, Thiomestron and thiophenolacetate on excretion kinetics and distribution pattern of 203Hg injected intravenously in a dose of 120 microgram 203Hg2+ per rat. A considerably enhanced biliary excretion of mercury was observed after pretreatment with Spironolactone, Unitiol, BAL and Thiomestron. The action of these agents persisted for only 2--3 hours after mercury application. The highest urinary excretion of mercury was recorded after pretreatment with Unitol and BAL. All the tested agents, particularly thiophenolacetate, turned out to enhance mercury excretion through intestinal wall cells. Pretreatment with the tested agents caused also considerable changes in the pattern of mercury distribution in the rat organism.
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PMID:Effect of some chelating agents on the biliary excretion of mercury. 1. Excretion kinetics and distribution of mercury in the organism. 744 Sep 69

Four chelating agents that have been used most commonly for the treatment of humans intoxicated with lead, mercury, arsenic or other heavy metals and metalloids are reviewed as to their advantages, disadvantages, metabolism and specificity. Of these, CaNa2EDTA and dimercaprol (British anti-lewisite, BAL) are becoming outmoded and can be expected to be replaced by meso-2,3-dimercaptosuccinic acid (DMSA, succimer) for treatment of lead intoxication and by the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS, Dimaval) for treating lead, mercury or arsenic intoxication. Meso-2,3-DMSA and DMPS are biotransformed differently in humans. More than 90% of the DMSA excreted in the urine is found in the form of a mixed disulfide in which each of the sulfur atoms of DMSA is in disulfide linkage with an L-cysteine molecule. After DMPS administration, however, acyclic and cyclic disulfides of DMPS are found in the urine. The Dimaval-mercury challenge test holds great promise as a diagnostic test for mercury exposure, especially for low level mercurialism. Urinary mercury after Dimaval challenge may be a better biomarker of low level mercurialism than unchallenged urinary mercury excretion.
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PMID:Mobilization of heavy metals by newer, therapeutically useful chelating agents. 771 89

1. We report two cases of acute mercury vapour intoxication in humans. The mercury vapour was released from smelting alloys (gold-mercury amalgam). The alloy was apparently contaminated with an unknown amount of mercury. 2. Within half an hour of the incident, the victims began having moderate headache, nausea, lumbar pain and shortness of breath at rest. The patients were treated with BAL (2,3 dimercaptopropanol), followed by DMSA (2,3 dimercaptosuccinic acid). 3. Serial measurements of mercury metal in plasma and in urine were made for ten days. 4. The results suggest that in spite of the treatment, relatively high concentrations of mercury remain in the plasma for a very long time, and this could be explained by the progressive release of mercury from red blood cells and tissues after oxidation. However, BAL and DMSA did not seem to be the most efficient antidotes. They reduce the plasma inorganic mercury uptake at concentrations of < 50 micrograms I-1.
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PMID:Elemental mercury vapour toxicity: treatment and levels in plasma and urine. 771 4

Factors affecting the renal uptake of inorganic mercury were investigated using primary cultures of rat renal cortical epithelial (RCE) cells under protein- and amino acid-free conditions. The cells were isolated from kidneys of adult rats and cultured. Confluence of culture (cell density), monitored morphologically and by total protein content, was achieved on Day 5. The RCE cells were incubated with 1 microM Hg at 37 degrees C for 30 min, followed by washing with phosphate-buffered saline containing various chelating agents (i.e., EGTA, PEN, DMSA, and BAL) to remove the surface-bound, noninternalized Hg. A substantial portion of Hg was bound to the cell surface. The removal of Hg from these binding sites was dependent on the stability constants of the chelating agents for Hg and lipophilic BAL removed the most Hg. Hg accumulation by the cells was dependent on cell density and decreased as the cell culture became confluent, possibly due to the formation of tight junctions resulting in a majority of the Hg transport occurring through the apical membrane. As measured after BAL washing, metabolic inhibitors, NaF, DNP, and ouabain decreased Hg accumulation by 28% and low temperature (4 degrees C) decreased it by 62%. Dependence of Hg uptake on metabolic energy and temperature suggests that a part of Hg is transported via active transport system. The pronounced decrease of Hg uptake at 4 degrees C indicates that, in addition to active transport, Hg transport also involves simple diffusion, some of which is dependent on membrane fluidity. It is concluded that Hg transport in RCE cells through the apical membrane occurs mainly by diffusion, and to a smaller extent by active transport.
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PMID:Mercury uptake by primary cultures of rat renal cortical epithelial cells. I. Effects of cell density, temperature, and metabolic inhibitors. 774 83

Chelating agents such as calcium disodium ethylenediaminetetraacetate (EDTA), 2,3-dimercaptopropanol (BAL), or D-penicillamine (D-PA) have been widely used for the past 4 decades as antidotes for the treatment of acute and chronic metal poisoning. In recent years, meso-2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercapto-1-propanesulfonate (DMPS) and sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron) have also shown to be effective to prevent against toxicity induced by a number of heavy metals. The purpose of the present article was to review the protective activity of various chelating agents against the embryotoxic and teratogenic effects of well-known developmental toxicants (arsenic, cadmium, lead, mercury, uranium, and vanadium). DMSA and DMPS were found to be effective in alleviating arsenate- and arsenite-induced teratogenesis, whereas BAL afforded only some protection against arsenic-induced embryo/fetal toxicity. Also, DMSA, DMPS, and Tiopronin were effective in ameliorating methyl mercury-induced developmental toxicity. Although the embryotoxic and teratogenic effects of vanadate were significantly reduced by Tiron, no significant amelioration of uranium-induced embryotoxicity was observed after treatment with this chelator.
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PMID:Prevention by chelating agents of metal-induced developmental toxicity. 779 20


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