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)

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

Contaminated puncture wounds were simulated in rat by intramuscular injection of 210Po. The aim of the study was to determine the effectiveness of chelation treatment as a function of time, dosage, and route of chelate administration. Ten newly synthesized substances containing vicinal sulphydryl and carbodithioate groups were used and their effect was compared with that of chelators clinically applicable in man--BAL (2,3-dimercaptopropane-1-ol), DMPS (2,3-dimercaptopropane-1-sulphonate), DMSA (meso-2,3-dimercaptosuccinic acid), and DDTC (sodium diethylamine-N-carbodithioate). The results indicate first that complete removal of 210Po from the injection site is achieved by only two local injections of DMPS, beginning as late as 2 h after injection of 210Po. Second, many of the substances used merely induce translocation of 210Po from the injection site into other tissues. Third, a combined local treatment at the injection site with DMPS plus repeated systemic, subcutaneous, treatments with HOEtTTC (N,N'-di-(2-hydroxyethyl)ethylenediamine-N,N-biscarbodithioate), a derivative of DDTC, results after 2 weeks in a reduction of the estimated total body retention of 210Po to about one-third of that in untreated controls. In the latter case the cumulative excretion of 210Po increased from 8 to 54%, mainly via the faeces.
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PMID:Combined chelation treatment for polonium after simulated wound contamination in rat. 759 64

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

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

Interactions of dithiols with p-aminophenyldichloroarsine (APA) and with Torpedo nicotinic receptors were studied using two approaches. First, the stability of dithiol-APA complexes in solution was studied based on quenching thiol reactions with dithiobis-(nitrobenzoic acid). A peptide corresponding to a portion of the Torpedo alpha-subunit and various 1,2-dithiols such as 2,3-dimercaptopropanesulfonic acid (DMPS), 2,3-dimercaptosuccinic acid formed stable complexes with APA, while 1,4-dithiols, such as dithiothreitol (DTT) and 2,5 dimercapto-N,N,N'N'-tetradipamide (DTA) did not. The Kd of APA association with DTT in Tris buffer is 2 microM. These data suggest that APA has greater affinity for reduced nicotinic receptors than for either DTT or DTA, a prediction that was experimentally confirmed, since these reagents do not reverse the effects of APA on nicotinic receptors. Second, application of DMPS and BAL, but not 2,3-dimercaptosuccinic acid, to DTT-treated receptors both reversed the effects of APA-receptor complexes and prevented alkylation by bromoacetylcholine, suggesting that DMPS and BAL "oxidize" reduced nicotinic receptors. The presence of air is required for this "oxidizing" effect, but no clear mechanism was discovered, since prevention of formation of the reactive oxygen species superoxide, hydrogen peroxide, or hydroxyl radicals failed to block oxidation. These data suggest that oxygen reacts with dithiols to produce unknown reactive species that directly oxidize reduced nicotinic receptors, although other interpretations are still possible.
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PMID:Interactions of dithiols with p-aminophenyldichloroarsine and nicotinic acetylcholine receptors. 805 Nov 36

1 Dimercaprol (BAL), 2,3-dimercaptopropanesulphonate sodium (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) are effective arsenic antidotes, but the question which one is preferable for optimal therapy of arsenic poisoning is still open to discussion. Major drawbacks of BAL include (a) its low therapeutic index, (b) its tendency to redistribute arsenic to brain and testes, for example, (c) the need for (painful) intramuscular injection and (d) its unpleasant odour. 2 The newer antidotes DMPS and DMSA feature low toxicity and high therapeutic index. They can be given orally or intravenously due to their high water solubility. While these advantages make it likely that DMPS and DMSA will replace BAL for the treatment of chronic arsenic poisoning, acute intoxication-especially with lipophilic organoarsenicals-may pose a problem for the hydrophilic antidotes, because their ionic nature can adversely affect intracellular availability. 3 This article focuses on aspects dealing with the power of BAL, DMPS, and DMSA to mobilize tissue-bound arsenic in various experimental models, such as monolayers of MDCK (= Madin-Darby canine kidney) cells from dog kidney, isolated perfused liver from guinea-pigs, and perfused jejunal segments from rat small intestine. 4 The results show that hydrophilic DMPS and DMSA may fail to rapidly and completely remove arsenic that has escaped from the extracellular space across tight epithelial barriers. However, owing to their low toxicity, which allows larger doses to be applied, and the potential modification of their pharmacokinetics by means of inert oral anion-exchange resins, DMPS and DMSA may advantageously replace BAL whenever intervention time is not critical. With severe intoxication by organic arsenicals, when the point-of-no-return is a limiting factor, BAL may still have a place as an arsenic antidote.
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PMID:Are we ready to replace dimercaprol (BAL) as an arsenic antidote? 929 86

The effectiveness of 2,3-dimercaptopropanol (BAL) and meso-2,3-dimercaptosuccinic acid (DMSA) on HgCl2-induced nephrotoxicity was studied in the rat. Seven groups of adult male rats were given a single sc toxic dose of HgCl2 (0.68 mg/kg) followed by 0.9% saline (positive control group), BAL (15, 30, and 60 mg/kg) or DMSA (50, 100, and 200 mg/kg) administered ip at 0, 24, 48, and 72 h thereafter. Although the renal function of HgCl2-exposed rats was slightly improved after BAL administration, Hg concentrations in the kidney were only reduced at 60 mg/kg. In addition, the protective effect of BAL was not dose-related. In contrast to BAL, DMSA was effective in increasing the urinary excretion of Hg and in reducing the renal Hg content. These results show that DMSA would be more effective than BAL in preventing or in protecting against inorganic Hg-induced nephrotoxicity.
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PMID:Comparison of the effectiveness of 2,3-dimercaptopropanol (BAL) and meso-2,3-dimercaptosuccinic acid (DMSA) as protective agents against mercuric chloride-induced nephrotoxicity in rats. 976 65

The therapeutic use of BAL (2,3-dimercaptopropanol) as treatment for poisoning has been halted by data suggesting serious neurotoxicity. This article is a report on the effects of BAL and other dithiols, DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercaptopropane-1-sulfonic acid), on [3H]glutamate release and uptake by rat brain synaptosomes and [3H]glutamate uptake by synaptic vesicles. BAL (100 microM) inhibited glutamate uptake (30%) and stimulated its basal release (30%) in synaptosomes, without affecting K+-stimulated release. BAL also inhibited glutamate uptake by synaptic vesicles (up to 60%). DMPS and DMSA (100 microM) had no significant effects on these parameters. The data reported here provide some evidence of glutamate involvement in BAL-induced neurotoxicity by demonstrating direct effects of BAL on glutamatergic system modulation.
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PMID:BAL modulates glutamate transport in synaptosomes and synaptic vesicles from rat brain. 1123 55

2,3-Dimercaptopropanol (BAL- British Anti-Lewesite) is a dithiol chelating agent used for the treatment of heavy metal poisoning, however, BAL can produce neurotoxic effects in a variety of situations. Based on the low therapeutic efficiency of BAL other dithiols were developed and DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercaptopropane-1-sulfonic acid) are becoming used for treatments of humans exposed to heavy metals. In the present investigation the effect of dithiols in the glutamatergic system was examined. The results showed that BAL inhibited [3H]MK-801 and [3H]glutamate binding in a concentration-dependent manner. At 100 microM BAL and DMSA caused a significantly inhibition of [3H]MK-801 binding to brain membranes (p < 0.05 by Duncan's multiple range test). BAL at 100 microM caused an inhibition of 40% on [3H]glutamate binding. DMPS and DMSA had no significant effect on [3H]glutamate binding. Dithiotreitol (DTT), abolished the inhibitory effect of BAL on [3H]MK-801 binding. The protection exerted by DTT suggests that BAL inhibit [3H]MK-801 binding by interacting with cysteinyl residues that are important for redox modulation of receptor responses. ZnCl2 inhibited [3H]glutamate and [3H]MK-801 binding to brain synaptic membrane; nevertheless, the inhibitory effect was slight more accentuated for [3H]MK-801 than [3H]glutamate binding (p < 0.05). The inhibition caused by 10 microM ZnCl2 on [3H]MK-801 binding was attenuated by BAL. The findings present in this study may provide the evidence that BAL affect the glutamatergic system and these effects can contributed to explain, at least in part, why BAL, in contrast to DMPS and DMSA is neurotoxic.
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PMID:Effect of dithiol chelating agents on [3H]MK-801 and [3H]glutamate binding to synaptic plasma membranes. 1188 82

Metals are amongst the oldest toxic substances known to man. In today's industrialized world the sources of exposure to metals are ubiquitous both in the field of work and from polluted water, foodstuffs and the environment. Their toxicity is characterized by the metallic element in question, but this is modified by the type of compound, whether organic or inorganic, and its characteristics of hydrosolubility and liposolubility, which determines its toxicokinetics and thus the possibilities of it reaching its targets. The biomolecules most affected by metals are the proteins with enzymatic activity, which is why their pathology is multisystemic. The principal systems affected are the gastrointestinal, central and peripheral neurological, haematic and renal. Some metallic compounds are carcinogenic. Metals's treatment is conditioned by their chemical reactivity. They can be deactivated and eliminated by the administering of chelating agents that produce complex molecules, which are non-toxic and can be excreted. The principal chelating agents are: BAL (British Anti-Lewisite or dimercaprol) DMPS (2,3-Dimercapto-1-propanesulfonic Acid) and DMSA (meso-2,3-Dimercaptosuccinic or Succimer), EDTA, Penicilamine (b,b-dimethylcysteine) and Deferoxamine. Toxicokinetic characteristics, mechanism of action, clinical picture and treatment of some of the most relevant metals and metalloids: lead, mercury and arsenic, are considered.
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PMID:[Metal poisoning]. 1281 82


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