Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 effects of some new chelating agents on the cadmium burden of CHO cells in culture were investigated. The chelators were sodium-N-(4-methoxybenzyl)-D-glucamine-dithiocarbamate (MeOBG-DTC), sodium-N-benzyl-D-glucaminedithiocarbamate (BG-DTC) and diisopropylmeso-2,3-dimercapto succinate (DiP-DMSA). The results were compared with the effect of the well known dimercaptopropanol (BAL). The derivates of dithiocarbamate are much less toxic than DiP-DMSA and BAL. All chelators effectively prevent Cd uptake into the cells. Mobilization of intracellular Cd, however, is more effective by the DTC-derivatives than by DiP-DMSA or BAL. Within the cell the major fraction of Cd after 48 hours incubation is found in the nuclei and cytosol and very little in the peroxisomes. The chelating agents remove the metal mostly from nuclei and cytosol. Incubation of the cells with cadmium leads to the induction of a Cd binding protein of an apparent molecular weight of 12500 Da, presumably metallothionein. MeOBG-DTC is more effective in removing the metal from this protein than BG-DTC.
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PMID:Effects of chelating agents on the cadmium burden of cells in culture. 165 37

Acute toxicity and the disposition of inorganic mercury depends on the route of exposure. Most previous studies on effect of chelators on inorganic mercury toxicity and toxicokinetics employed parenteral administration of both metal and chelator. However, the most prominent routes for human inorganic mercury exposure are the oral or pulmonary. BAL was previously considered the drug of choice in human intoxications with most heavy metals. This recommendation has been questioned during recent years due to the advent of the less toxic hydrophilic BAL analogues DMSA and DMPS. The present study, using oral administration of HgCl2 labelled with 203Hg, demonstrates that DMPS is superior to the other chelators in preventing mortality. Moreover, both DMSA and DMPS are superior to BAL and NAPA in alleviating acute toxicity and in preventing the undesirable distribution of orally administered mercury, especially to the brain. Further, oral administration of these chelators were more efficient than parenteral administration in reducing whole-body retention and organ deposition of orally administered mercuric chloride, most likely due to the prevention of intestinal uptake of mercury.
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PMID:Effect of four thiol-containing chelators on disposition of orally administered mercuric chloride. 168 54

1 The standard drug for the treatment of arsenic poisoning is BAL (dimercaprol). BAL possesses marked side-effects and a low safety ratio, drawbacks which new BAL analogues, DMPS and DMSA, do not possess. 2 The efficacy of three chelating agents, BAL, DMPS and DMSA, has been evaluated as a treatment for systemic organic arsenic poisoning, induced by intravenous dichloro(2-chlorovinyl)arsine (lewisite) administration to rabbits. Equimolar dosing schedules were used based upon realistic doses for the most toxic agent, BAL. 3 It was concluded that all three dimercapto chelating agents provided significant protection against the lethal systemic effects of lewisite, and, under the test conditions reported here, there was no significant difference between them in therapeutic efficacy. 4 The cause of mortality following intravenous lewisite in treated and untreated rabbits was pulmonary damage. 5 It is considered that DMPS and DMSA are worthy of further study as replacements for BAL in the treatment of systemic poisoning by lewisite.
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PMID:Evaluation of the efficacy of dimercapto chelating agents for the treatment of systemic organic arsenic poisoning in rabbits. 216 7

Proton nuclear magnetic resonance spectroscopy was used to determine relative binding constants for several arsenical-antidote adducts. It was found that BAL (2,3-dimercaptopropanol) and DMPS (2,3-dimercaptopropanesulfonic acid) had a higher affinity than DMSA (2,3-dimercaptosuccinic acid) for the two organic arsenicals studied.
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PMID:Relative binding constants of arsenical-antidote adducts determined by NMR spectroscopy. 217 85

British antilewisite (2,3-dimercaptopropanol; BAL) has long been used as an arsenic antidote, but its therapeutic efficacy is limited by its inherent toxicity. We synthesized two less toxic derivatives of BAL and investigated their potential as antidotes to organic arsenic. The new compounds, 2,3-dithioerythritol (DTE) and 2,2-dimethyl-4-(hydroxymethyl)-1,3-dithiolane (isopropylidene derivative of BAL), react readily with phenyldichloroarsine (PDA) to yield the expected corresponding cyclic 1,3-dithioarsolanes. The BAL derivatives were compared to BAL in terms of their cytotoxicity and their ability to rescue PDA-poisoned mouse lymphoma cells in culture. The dithiolane was not a good antidote in the cultured cell system. In contrast, DTE was less toxic than BAL or DMSA and was superior at improving cell survival in PDA-exposed cells.
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PMID:2,3-Dithioerythritol, a possible new arsenic antidote. 256 24

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

Chelating agent, such as CaEDTA, CaDTPA, D-penicillamine, DMSA, desferoxamine, NTA, cysteine ethyl ester, BAL, alpha-MPG, phthalein complexone, were tested as a possible contrast enhancing agent for tumor imaging with 67Ga-citrate. The intravenous administration of a chelating agent to Ehrlich's tumor bearing mice, one hour after the injection of 67Ga-citrate, accelerated the blood clearance with only a very slight change of activity in the target, increasing the tumor-to-blood ratio, and consequently achieving a better visualization. Among the tested chelating agents, D-penicillamine showed the highest target-to-nontarget ratio at a shorter time: a good tumor-to-blood ratio, performed after 24 hr with non-treated animals, was achieved in only 1-3 hr with post-treated animals. Thus, D-penicillamine hold a considerable promise as a contrast enhancing agent for future clinical use.
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PMID:[Enhancement of 67Ga tumor-to-blood ratios by chelating agent (author's transl)]. 737 79

It has been shown that oxophenylarsine (PhAsO) inhibits glucose uptake in MDCK cells. In addition to the known impairment of cellular energy metabolism, this inhibition may contribute to the acute toxicity of trivalent organic arsenicals. We have investigated the effect of BAL, DMPS, DMSA, and other sulfur compounds on cellular incorporation of [U-14C]PhAsO and their efficacy to revert PhAsO-induced inhibition of glucose uptake. In the presence of [U-14C]PhAsO (2 microM), the radiolabel was steadily accumulated by the cells over 150 min without any signs of severe cell damage (e.g., altered morphology, increased LDH release). A notable decrease of cellular ATP was only observed at 150 min, whereas within 30 min uptake of D-[6-(14)C]glucose was reduced to 40% of controls. When BAL, DMPS, or DMSA was added after 30 min, the inhibition of glucose uptake was reversed, accompanied by a decrease in cell-associated radiolabel from [U-14C]-PhAsO. Water-soluble DMPS and DMSA required longer times than BAL for comparable effects. 2,3-Bis(acetylthio)propanesulfonamide, a thioester derivative, and dithiothreitol, a 1,4-dithiol, were effective only with the highest concentration tested (200 microM). 2-Mercaptoethanol neither reversed inhibition of glucose uptake nor influenced [U-14C]PhAsO incorporation. Our results show that inhibition of glucose uptake is a very early event in PhAsO cytotoxicity which occurs before any decrease of cellular energy metabolism and/or full cellular loading with arsenic comes into effect. The more rapid onset of action of lipophilic BAL compared to PhAsO action.
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PMID:Reversal of oxophenylarsine-induced inhibition of glucose uptake in MDCK cells. 758 19

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


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