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)

Arsenic (As2O3)-poisoned rats were treated with either 2,3-dimercaptosuccinic acid (DMS) or dimercaptopropanol (BAL) at doses of 30 mg/kg/day. A control group received no treatment. The total quantity of arsenic excreted was not significantly different in response to 4 days of treatment with either DMS or BAL. In addition, there was no difference between the two drug treatment groups in the residual arsenic content of brain, liver, kidney and spleen after treatment. Both drugs reduced the arsenic content of each tissue to approximately 40% of that of untreated controls. Previous studies have shown that DMS is orally effective for the treatment of lead poisoning. The LD50 of DMS was determined to be in excess of 3 g/kg in rats and mice, approximately 30 times the LD50 of BAL. No gross, histopathological or biochemical evidence of toxicity was observed in mice, rats or dogs which received DMS 5 days per week for 6 months. DMS did not affect the excretion of zinc, iron, calcium or magnesium. Urinary copper excretion was significantly elevated in response to 30 mg/kg of DMS, suggesting that the drug might also be useful for the treatment of Wilson's disease.
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PMID:The pharmacology of 2,3-dimercaptosuccinic acid and its potential use in arsenic poisoning. 21 41

2,3-Dimercaptosuccinic acid (DMSA) an investigational chelant structurally similar to dimercaptopropanol (BAL), offers the advantage of not depleting iron stores on which basis it would not seem to form a toxic chelate with iron. We report the case of a man with a formidable body burden of lead (Pb) and depleted iron stores who was given iron intramuscularly during a defined period of long-term retreatment with DMSA. Initiation of retreatment with DMSA, 30 mg/kg/day given orally in three divided doses for the first 7 days markedly enhanced Pb diuresis, entailed a pronounced fall in blood Pb and abolished symptoms of Pb poisoning. Continuation of retreatment with two-thirds the initial DMSA dose for an added 15 days maintained blood Pb at sustained low levels. Iron sorbitol administered intramuscularly during this period in individual doses of 100 mg of elemental iron given 3 days apart to a conservative total of 400 mg produced no untoward effects, suggesting that a toxic chelate between iron and DMSA was not formed. Serum ferritin entered the normal range and there was virtually an immediate significant decrease in erythrocyte protoporphyrin. Together with discernible increases in haemoglobin, haematocrit and MCV, this pointed to enhanced iron utilization. Since iron utilization is curtailed by high concentrations of Pb, the immediacy and magnitude of the post-chelation rebound in blood Pb precluded iron administration at any other stage. From these data, DMSA emerges as a uniquely versatile new chelant. Suitable for long-term administration, it permits the simultaneous parenteral administration of iron during dose-related sustained decreases in blood Pb.
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PMID:Intramuscular administration of iron during long-term chelation therapy with 2,3-dimercaptosuccinic acid in a man with severe lead poisoning. 254 23

One of us has previously reported that treatment of the Keilin and Hartree heart-muscle preparation with 2,3-dimercaptopropanol (BAL), in the presence of air, leads to the complete inactivation of the succinate oxidase system with little if any effect on the activities of succinate dehydrogenase (until more than half the BAL was oxidized) or cytochrome c oxidase. The inactivation of the complete succinate oxidase system requires the oxidation of BAL by air in the presence of the enzyme. It is not caused by H2O2 or BAL disulphides produced during the oxidation of BAL. Spectroscopic studies identified the block as lying between cytochromes b and c. It was suggested that a BAL-labile factor is present which transfers electrons from cytochrome b to cytochrome c and which is destroyed by coupled oxidation with BAL. The factor is also required for NADH oxidation. Subsequent work showed it is not identical with cytochrome c1 (ref. 4), myoglobin present in the preparation or the antimycin-binding site. We report here that this factor is identical to the iron-sulphur protein in the central portion of the respiratory chain first identified by Rieske.
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PMID:Identification of the BAL-labile factor. 625 40

1 A survey is given of the use of chelating agents in the treatment of metal poisonings. 1 The complexing agents in established clinical use are the polyaminopolycarboxylic acid EDTA (ethylenediamine tetraacetate) and the thiols BAL (2, 3-dimercaptopropanol) and D-penicillamine. Desferrioxamine is useful in the treatment of iron overloading. 2 The theoretical foundation of the metal-ligand interaction and some general principles of value in the search for new metal antidotes are outlined. 3 Recent research has shown that 2, 3-dimercaptosuccinic acid (DMS) and 2, 3-dimercaptopropane-1-sulphonate (DMPS) are effective in mercury and arsenic poisonings. 4 DMS and DMPS are of significantly lower toxicity than BAL, and they can be administered orally or intravenously. 5 A particularly low toxicity of DMS is reported from clinical and experimental studies, and this agent may be useful against several metal poisonings including mercury, lead and gold.
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PMID:Recent advance in the therapy of metal poisonings with chelating agents. 634 41

A new strictly anaerobic bacterium (strain BAL-1T) has been isolated from a reed bed at Ballarat Goldfields in Australia. The organism grew by reducing arsenate [As(V)] to arsenite [As(III)], using acetate as the electron donor and carbon source; acetate alone did not support growth. When BAL-1T was grown with arsenate as the terminal electron acceptor, acetate could be replaced by pyruvate, L- and D-lactate, succinate, malate, and fumarate but not by H2, formate, citrate, glutamate, other amino acids, sugars, or benzoate. When acetate was the electron donor, arsenate could be replaced by nitrate or nitrite but not by sulfate, thiosulfate, or iron oxide. Nitrate was reduced to ammonia via nitrite. The doubling time for growth on acetate (5 mM) plus arsenate (5 mM) or nitrate (5 mM) was 4 h. The G+C content of the DNA is 49 mol%. The 16S rRNA sequence data for the organism support the hypothesis that this organism is phylogenetically unique and at present is the first representative of a new deeply branching lineage of the Bacteria. This organism is described as Chrysiogenes arsenatis gen. nov., sp. nov.
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PMID:Chrysiogenes arsenatis gen. nov., sp. nov., a new arsenate-respiring bacterium isolated from gold mine wastewater. 886 50

Lung transplantation has become a therapeutic option for end-stage pulmonary diseases, but after transplantation, infections and obliterative bronchiolitis (OB) are major causes of long-term morbidity and mortality. OB is a fibroproliferative disease, of poorly understood etiology, characterized by an irreversible decline in allograft function. Because diseases with tissue iron overload are characterized by fibrosis and end-organ failure, we studied the iron concentrations in BAL fluid and lung tissue in 10 lung allograft patients. BAL fluid revealed significantly elevated iron concentrations in allograft patients compared with five normal volunteers (135+/-16.54 micromol/L vs 33.65+/-7.48 micromol/L, respectively). Prussian blue staining of biopsy specimens of lung allograft tissue revealed an accumulation of iron primarily in alveolar macrophages. Immunohistochemical stains for ferritin revealed accumulation of the protein in macrophages, interstitium, vascular walls, and bronchiolar epithelium. Iron studies of the blood (serum ferritin and iron concentrations) revealed no evidence for systemic iron overload. In conclusion, patients with pulmonary allografts appear to have elevated concentrations of iron in lung tissue. This iron overload may place the allografts at increased risk of metal-mediated injury and fibrosis.
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PMID:Iron accumulation in lung allografts after transplantation. 926 81

Copper is an essential trace element, which is an important catalyst for heme synthesis and iron absorption. Following zinc and iron, copper is the third most abundant trace element in the body. Copper is a noble metal, like silver and gold. Useful industrial properties include high thermal and electrical conductivity, low corrosion, alloying ability, and malleability. Most of the metallic copper appears in electrical applications. Copper is a constituent of intrauterine contraceptive devices and the release of copper is necessary for their contraceptive effects. The average daily intake of copper in the US is about 1 mg Cu with the primary source being the diet. The bioavailability of copper from the diet is about 65-70% depending on a variety of factors including chemical form, interaction with other metals, and dietary components. The biological half-life of copper from the diet is 13-33 days with bilary excretion being the major route of elimination. Copper sulfate is a gastric irritant that produces erosion of the lining of the gastrointestinal tract. Chronic copper toxicity is rare and primarily affects the liver. Wilson's disease and Indian childhood cirrhosis are examples of severe chronic liver disease that results from the genetic predisposition to the hepatic accumulation of copper. The serum copper concentration ranges up to approximately 1.5 mg/L in healthy persons. Gastrointestinal symptoms occur at whole blood concentrations near 3 mg Cu/L. Chelating agents (CaNa2EDTA, BAL) are recommended in severe poisoning, but there are little pharmacokinetic data to evaluate the effectiveness of these agents.
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PMID:Copper. 1038 57

The effect of tetrathiomolybdate (TM), disodium calcium ethylenediamine tetraacetate (EDTA), D-penicillamine (PEN), 2-3 dimercapto-1-propanol (BAL) and dimethyl dithiocarbamate (DDC) administration on biliary and urinary excretion of copper (Cu), zinc (Zn) and iron (Fe) was investigated in sheep on a low Cu diet (Group A) and a high Cu diet (Group B). Only biliary Cu excretion increased significantly (P<0.01) with TM treatment. Urinary Cu excretion increased (P<0.01) following PEN treatment. TM, EDTA, PEN, BAL and DDC adminstration increased Cu excretion via bile and urine by 254, 11, 266, 46 and 16%, respectively in Group A sheep, and by 354, 13, 196, 20 and (-) 31% in Group B sheep. Urinary Zn excretion increased (P<0.01) following EDTA and PEN treatments. Only urinary Fe excretion increased (P<0.01) with EDTA treatment. The results show that TM and PEN are the most efficient decoppering agents, but PEN unlike TM also removes Zn. The major routes of excretion of Cu chelates by TM and PEN are different. TM increases Cu excretion significantly (P<0.05 in Group A and P<0.01 in Group B) in bile with only a slight increase in urinary Cu whereas PEN increases Cu excretion significantly (P<0.01) in urine. Therefore from a therapeutic view, a combination therapy of TM and PEN would be useful to maximize Cu removal from the body.
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PMID:Effect of chelating agents on the excretion of copper, zinc and iron in the bile and urine of sheep. 1246 2

Impact of blast shock waves (SW) with the body wall produces blast lung injuries characterized by bilateral traumatic hemorrhages. Such injuries often have no external signs, are difficult to diagnose, and therefore, are frequently underestimated. Predictive assessment of acute respiratory distress syndrome outcome in SW-related accidents should be based on experimental data from appropriate animal models. Blood plasma transferrin is a major carrier of blood iron essential for proliferative "emergency" response of hematopoietic and immune systems as well as injured tissue in major trauma. Iron-transferrin complexes (Fe3+ TRF) can be quantitatively analyzed in blood and tissue samples with low-temperature EPR techniques. We hypothesized that use of EPR techniques in combination with assays for pro-inflammatory cytokines and granulocytes in the peripheral blood and BAL would reveal a pattern of systemic sequestration of (Fe3+)TRF that could be useful for development of biomarkers of the systemic inflammatory response to lung injury. With this goal we (i) analyzed time-dependent dynamics of (Fe3+)TRF in the peripheral blood of rats after impacts of SW generated in a laboratory shock-tube and (ii) assayed the fluctuation of granulocyte (PMN) counts and expression of CD11b adhesion molecules on the surface of PMNs during the first 24 h after SW induced injury. Sham-treated animals were used as control. Exposure to SW led to a significant decrease in the amount of blood (Fe3+)TRF that correlated with the extent of lung injury and developed gradually during the first 24 h. Thus, sequestration of (Fe3+)TRF occurred as early as 3 h post-exposure. At that time, the steady state concentration of (Fe3+)TRF in blood samples decreased from 19.7+/-0.6 microM in controls to 7.5+/-1.3 microM in exposed animals. The levels of (Fe3+)TRF remained decreased throughout the entire study period. PMN counts increased 5-fold and 3.5-fold over controls respectively, at 3 and 6 h postexposure. These effects were accompanied by an increase in expression of CD11b on the surface membrane of PMNs. Extensive release of cytokines IL-1, IL-6, MCP-1, and MIP-2 was observed in BAL fluid and blood plasma during 24 h postexposure. We conclude that EPR monitoring of blood (Fe3+)TRF can be a useful approach for assessment of systemic pro-inflammatory alterations due to SW-induced lung injury.
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PMID:Pro-inflammatory alterations and status of blood plasma iron in a model of blast-induced lung trauma. 1616 36

The effects of chelating drugs used clinically as antidotes to metal toxicity are reviewed. Human exposure to a number of metals such as lead, cadmium, mercury, manganese, aluminum, iron, copper, thallium, arsenic, chromium, nickel and platinum may lead to toxic effects, which are different for each metal. Similarly the pharmacokinetic data, clinical use and adverse effects of most of the chelating drugs used in human metal poisoning are also different for each chelating drug. The chelating drugs with worldwide application are dimercaprol (BAL), succimer (meso-DMSA), unithiol (DMPS), D-penicillamine (DPA), N-acetyl-D-penicillamine (NAPA), calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA), calcium trisodium or zinc trisodium diethylenetriaminepentaacetate (CaNa(3)DTPA, ZnNa(3)DTPA), deferoxamine (DFO), deferiprone (L1), triethylenetetraamine (trientine), N-acetylcysteine (NAC), and Prussian blue (PB). Several new synthetic homologues and experimental chelating agents have been designed and tested in vivo for their metal binding effects. These include three groups of synthetic chelators, namely the polyaminopolycarboxylic acids (EDTA and DTPA), the derivatives of BAL (DMPS, DMSA and mono- and dialkylesters of DMSA) and the carbodithioates. Many factors have been shown to affect the efficacy of the chelation treatment in metal poisoning. Within this context it has been shown in experiments using young and adult animals that metal toxicity and chelation effects could be influenced by age. These findings may have a bearing in the design of new therapeutic chelation protocols for metal toxicity.
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PMID:Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. 1630 72


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