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 effect of several chelating agents (diethyldithiocarbamic acid, DDC; nitrilotriacetic acid, NTA; 2,3-dimercaptopropanol, BAL; d,l-penicillamine, PEN; 2,3-dimercaptosuccinic acid, DMSA; ethylenediaminetetraacetic acid, EDTA; and diethylenetriaminepentaacetic acid, DTPA) on the toxicity, distribution and excretion of cadmium (Cd) was determined in mice. When chelators were administered immediately after Cd, significant increases in survival were noted after treatment with DMSA, EDTA, and DTPA. DTPA, followed by EDTA and then DMSA, were consistently the most effective in decreasing the tissue concentrations of Cd and increasing the excretion of Cd. NTA, BAL, DDC and PEN had no beneficial effects. The effects of increasing the time interval between Cd administration and initiation of chelation therapy was determined by using a single administration of DTPA, EDTA, and DMSA. Mice treated immediately after Cd administration excreted approximately 50% of the administered dose of Cd compared to 0.2% in controls. Treatment with chelator at later times significantly increased Cd excretion but the magnitude of the effect was much less than that seen in mice treated immediately after Cd. To determine the role of MT in the acute decrease in chelator efficacy following Cd poisoning, rats were injected IV with Cd followed by DTPA at various times after Cd. Although DTPA reduced Cd content in the various organs when given immediately after Cd, the chelator was ineffective at all later times. Increases in hepatic and renal metallothionein (MT) did not occur until 2 hr after Cd, and did not coincide with the earlier drop in chelator efficacy. Blockade of MT synthesis by actinomycin D failed to eliminate this decreased DTPA effectiveness. Therefore, it appears that MT does not play an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The effect of repeated daily administration of chelators on the distribution and excretion of Cd was studied by administering chelators daily for 5 days starting 48 hr after Cd. DTPA, EDTA, DMSA and BAL significantly increased the urinary elimination of Cd. Thus, mobilization of Cd into urine occurs with repeated chelation therapy, which may decrease tissue concentrations of Cd and reduce the toxicity of the metal.
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PMID:Alteration of tissue disposition of cadmium by chelating agents. 673 58

The utility of isolated rat hepatocytes as a model system for screening potential chelators in treatment of Cd intoxication was studied. The ability of the chelators diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA), 2,3-dimercaptosuccinic acid (DMSA), diethyldithiocarbamic acid (DDC), d,1-penicillamine (PEN), nitrilotriacetic acid (NTA), and 2,3-dimercaptopropanol (BAL) to decrease the cellular concentration of Cd was correlated with the previously reported effectiveness of these agents in the treatment of Cd intoxication in vivo. The results of cellular studies with either control or metallothionein-induced hepatocytes were compared to the in vivo effect of the chelators administered before or after the induction of metallothionein, respectively. The effects of DTPA, EDTA, DDC, and BAL in the hepatocyte model screening system correlated well with their reported in vivo effects. The results with NTA, PEN, and DMSA were not correlated as well but were explained by the relative differences between in vivo doses versus in vitro concentrations of the respective chelators. Therefore, the proposed model for screening potential chelators for use in cadmium intoxication appears to be a system which may prove to be an economical and rapid method to facilitate the search for efficacious chelators.
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PMID:Isolated rat hepatocytes as a model system for screening chelators for use in cadmium intoxication. 683 80

Cells cultures have been used to study the effect of 6 different metal chelating compounds on the efflux of Cadmium (Cd) from the cells and on cell growth. The cells had previously been made resistant to high levels of Cd (100 mumol/1) in the medium. They contain large amounts of intracellular Cd (40-50 nmol Cd/mg cell protein), the main part of which is bound to cytoplasmic metallothionein. Among the different monothiol and dithiol compounds tested are some old, well-known and to some extent therapeutically tried substances, i.e. 2,3-dimercapto-1-propanol (BAL), D-penicillamine (PA), N-acetyl-DL-penicillamine (NAPA) and some newer metal chelators, i.e. 2,3-dimercaptopropane-1-sulphonate (BAL-Sulph), mercaptosuccinic acid (MSA) and meso-2,3-dimercaptosuccinic acid (DMSA). The three latter ones all showed better effect on the egress of Cd than PA and NAPA and less toxic effect than BAL on an equimolar basis. All the agents tested increased the efflux of Cd from metallothionein-containing cell cultures which seem to be justified as a test system for primary screening of effect and toxicity of new chelators.
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PMID:Influence of certain chelating agents on egress of cadmium from cultured epithelial cells containing high amounts of metallothionein: a screening of Cd-releasing and toxic effects. 734 85

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


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