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 toxicity of cadmium is determined by chelation reactions: in vivo, Cd2+ exists exclusively in coordination complexes with biological ligands, or with administered chelating agents. The Cd2+ ion has some soft character, but it is not a typical soft ion. It has a high degree of polarizability, and its complexes with soft ligands have predominantly covalent bond characteristics. Cd2+ forms the most stable complexes with soft donor atoms (S much greater than N greater than 0). The coordination stereochemistry of Cd2+ is unusually varied, including coordination numbers from 2 to 8. Even though the Cd2+ ion is a d10 ion, disturbed coordination geometries are often seen. Generally, the stability of complexes increases with the number of coordination groups contributed by the ligand; consequently, complexes of Cd2+ with polydentate ligands containing SH groups are very stable. Cd2+ in metallothionein (MT) is coordinated with 4 thiolate groups, and the log stability constant is estimated to 25.5. Complexes between Cd2+ and low molecular weight monodentate or bidentate ligands, e.g., free amino acids (LMW-Cd), seem to exist very briefly, and Cd2+ is rapidly bound to high molecular weight proteins, mainly serum albumin. These complexes (HMW-Cd) are rapidly scavenged from blood, mainly by the liver, and Cd2+ is redistributed to MT. After about 1 day the Cd-MT complex (MT-Cd) almost exclusively accounts for the total retained dose of Cd2+, independent of the route of exposure. MT-Cd is slowly transferred to and accumulated in kidney cortex. The acute toxicity and interorgan distribution of parenterally administered Cd2+ are strongly influenced by preceding MT induction, or decreased capacity for MT synthesis; however, the gastrointestinal (GI) uptake of Cd2+ seems unaffected by preceding MT induction resulting in considerable capacity for Cd2+ chelation in intestinal mucosa, and this finding indicates that endogenous MT is not involved in Cd2+ absorption. The toxicity of parenterally administered Cd2+ is strongly enhanced when administered as complexes with NTA or STPP , but it is much decreased when administered as a complex with EDTA. In chronic oral exposure the toxicity and GI uptake of Cd2+ is not changed when Cd2+ is administered as a complex with the detergent formula chelating agents NTA, EDTA and STPP . The uptake of Cd2+ from ligated intestine in vivo was not affected by administration of Cd2+ as complexes with CYS or GSH, but significantly reduced by complexation with EDTA or BAL. The acute toxicity of orally administered Cd2+ is reduced when Cd2+ is administered as a complex with EDTA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chelation of cadmium. 673 60

Sulfhydryl substances (cysteine, glutathione, cysteamine and BAL) provide protection against experimental gastric ulcer induced by indomethacin while being ulcerogenous in stress-ulcer. Experimental data indicate the necessity to distinguish between "real" and "occasional" cytoprotective drugs.
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PMID:On the cytoprotective action of sulfhydryl-containing substances. 718 55

The rate of Cd accumulation by adult rat liver parenchymal cells in serum free primary culture in the presence of 100 microM CdCl2 was 10 times greater than that by non-parenchymal Kupffer cells. Addition of the monothiol chelating agents, cysteine and penicillamine, decreased Cd uptake in both cell types, the effect becoming more pronounced as the monothiol concentration was increased from 0.1 to 1.0 mM. These monothiols thus appear to reduce the availability of Cd for transport across the cell membrane. In contrast 1-10 molar excesses of the dithiol agents 2,3-dimercaptopropanol (BAL) or dithiothreitol (DTT) stimulated to variable extents the rate of Cd accumulation 2-10-fold in parenchymal cells and by over 100-fold in Kupffer cells. Supplementation of the media with 3% serum had little effect on the Cd accumulation in the presence of dithiols. Intravenous injection of Cd (0.05 mg/kg DCdCl2) with up to a 10-fold molar excess of cysteine or penicillamine had little effect on the hepatocellular Cd distribution. However Cd uptake by non-parenchymal cells was increased markedly by the simultaneous administration of BAL or DTT in 2 or 10 molar excess. Evidence is provided that these results may be partially explained by the endocytosis, particularly in Kupffer cells, of colloidal complexes of Cd which are formed with the dithiols but not the monothiols. These observations demonstrate that the physicochemical form of Cd determines its hepatocellular distribution which may be an important factor in the manifestation of Cd toxicity after thiol treatment.
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PMID:Effects of thiol agents on the accumulation of cadmium by rat liver parenchymal and Kupffer cells. 729 98

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

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

The effects of changes in sulfur-containing intracellular ligands on biliary excretion of cadmium were studied in rats. Injection of zinc or copper salts 24 h before intravenous injection of 109CdCl2 (1 mg/kg Cd) decreased biliary excretion of Cd. Pretreatment with cysteine (25 mg/kg) had a similar effect. Depletion of intracellular thiol by injection of diethylmaleate had little effect. The effect of chelating agents on the pharmacokinetics of Cd depended on time of administration of the agents after exposure to Cd. When chelating agents were administered 1/2 h after Cd injection (before the synthesis of metallothionein), the thiol-containing agents (2,3-dimercapto-1-propanol (BAL), DL-penicillamine, N-acetylpenicillamine, and dithioerythritol) increased the biliary excretion of Cd, while the carboxyl-containing ones (EDTA and nitrilotriacetate) increased the urinary excretion of Cd. BAL was the most effective chelating agent, but there was also an increase in the renal concentration of Cd. However, when these chelating agents were administered 24 h after Cd injection (after the synthesis of metallothionein), only BAL increased the biliary excretion of Cd. Renal and hepatic Cd concentrations decreased concurrently after BAL treatment.
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PMID:Biliary excretion of cadmium in rat. III. Effects of chelating agents and change in intracellular thiol content on biliary transport and tissue distribution of cadmium. 739 99

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

The rate of reaction of several radioprotective agents or their active metabolites with 4-hydroxynonenal (4HNE) was studied and compared to the rate of reaction with cysteine (Cys) and glutathione (GSH). The agents studied were: mercapto ethylamine (MEA); 2(3-aminopropyl) aminoethanethiol (WR1065); S-2-aminoethylisothiouronium bromide-hydrobromide (AET); 1,4-dithiothreitol (DTT); 1,4-dithioerythritol (DTE); N-2(2-mercaptopropionyl)-glycine (MPG); penicillamine hydrochloride (PA); N-acetylcysteine (NAC); 2-3 dimercapto-1 propane sulfonic acid (DMPS); 2,3-dimercaptopropanol (BAL), and meso 2,3 dimercapto succinic acid (DMS). All of them reacted with 4HNE. MEA and WR1065 were the most reactive thiols, and PA and DMS were the least reactive thiols. All the others reacted at rates comparable to or higher than that of cysteine or GSH. The potential role of this type of interactions in the protective action of these drugs against deleterious effects of radiation or carbon tetrachloride is analyzed.
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PMID:Reaction of 4-hydroxynonenal with some thiol-containing radioprotective agents or their active metabolites. 786 76


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