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 embryotoxic and teratogenic effects of methylmercury in experimental animals have been established by several investigators. The protective activity of 2,3-dimercaptopropanol (BAL) and sodium 2,3-dimercaptopropane-1-sulfonate (DMPS, a chelator used in the treatment of inorganic and organic mercury) on methylmercury chloride (MMC)-induced maternal and developmental toxicity in mice has been evaluated in the present study. BAL and DMPS were administered subcutaneously or by gavage to pregnant mice immediately after a single oral administration of 30 mg MMC/kg given on day 10 of gestation and at 24, 48, and 72 h thereafter. Amelioration by BAL and DMPS of MMC embryo/fetotoxicity was assessed at 15, 30, and 60 mg/kg/day and at 90, 180, and 350 mg/kg/day, respectively. Treatment with BAL did not ameliorate the maternal toxicity or the developmental toxicity of MMC observed in the mouse. In contrast, DMPS at 90, 180, and 360 mg/kg/day significantly reduced the maternal lethality of MMC, whereas treatment with 180 and 360 mg DMPS/kg/day showed significant protective activity against MMC-induced embryotoxicity and teratogenicity. Based on the present findings, DMPS might be a useful chelator against the maternal and developmental toxicity induced by methylmercury.
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PMID:Evaluation of the protective activity of 2,3-dimercaptopropanol and sodium 2,3-dimercaptopropane-1-sulfonate on methylmercury-induced developmental toxicity in mice. 811 25

A case of severe mercuric chloride poisoning with clinical signs of mucosal damage of the gastrointestinal tract and anuric renal failure, is presented. The initial whole blood mercury concentration was 14,300 micrograms l-1. This concentration is supposed to be associated with fatal outcome due to multiple organ failure. Because of anuric renal failure, haemodialysis was necessary. Kidney function returned to normal within 10 days. Haemodialysis proved to be ineffective with regard to total mercury elimination. Treatment with DMPS was started because of very severe poisoning, anuric renal failure and optimistic reports on the "new" chelating agent 2,3-dimercapto-1 propanesulphonic acid (DMPS) in mercury poisoning. DMPS was administered by parenteral route initially and was continued thereafter by oral route, until whole blood and urine mercury concentrations had decreased below a level considered as toxic. Except for a temporary pruritic erythema of the skin, no side effects of DMPS treatment were observed. The clinical course was mild, despite continuing high whole blood mercury concentrations. Recovery was uneventful and complete. DMPS treatment, administered by intravenous and oral route, was shown to be an effective alternative for BAL in life-threatening mercuric chloride intoxication. The pharmacokinetic data presented in this case report suggest that non-renal mercury clearance may considerably exceed renal mercury clearance.
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PMID:Mercury kinetics in a case of severe mercuric chloride poisoning treated with dimercapto-1-propane sulphonate (DMPS). 819 24

The effects of three chelating agents, N-benzyl-D-glucamine dithiocarbamate (BGD), 2,3-dimercaptopropanol (BAL) and D-penicillamine (D-PEN), on the excretion of mercury in rats exposed to mercuric chloride (HgCl2), the chemical forms of mercury compounds excreted in the bile and urine and the intestinal reabsorption of mercury compounds in the bile were studied. Rats were injected intraperitoneally with 203HgCl2 (300 micrograms Hg and 74 kBq of 203Hg/kg) and 24 h later, they were injected intraperitoneally with a chelating agent (a quarter of an LD50). The injection of the chelating agents significantly enhanced the biliary and urinary excretions of mercury. The enhancing effect of BGD on the excretions of mercury was almost the same as that of BAL and much larger than that of D-PEN. The major chemical form of mercury in the bile and urine of rats injected with BGD after HgCl2 treatment was Hg-BGD compounds. The chemical form of mercury in the bile and urine of rats injected with BAL after HgCl2 treatment was mainly Hg-GSH compound. The mercury after HgCl2 and D-PEN treatment was excreted mainly via the urine in the form of Hg-D-PEN compound. The intestinal reabsorption of mercury from the bile of rats injected with BGD or D-PEN was only 0.18% or 0.38% of the dose, respectively. The intestinal reabsorption of mercury from the bile of rats injected with BAL was 27.38% of the dose. It was suggested that the Hg-GSH compound excreted in the bile after HgCl2 and BAL treatment is partly degraded to Hg-cysteine (Cys) by the intestinal membranous enzymes and that the ligand of Hg-Cys is replaced by BAL in the bile, resulting in the effective reabsorption of Hg-BAL compound from the intestine.
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PMID:Further study of effects of chelating agents on excretion of inorganic mercury in rats. 844 11

A 17 year-old boy was admitted to the hospital because of severe hypertension (200/130 mmHg), headache, irritability, and sweating. Initial biochemical tests suggested pheochromocytoma, being treated with nifedipine, clonidine and propranolol. However, with report of exposure to mercury vapor, twenty-four-hour urine screening and measurement of blood mercury confirmed intoxication. The patient underwent courses of chelation therapy with dimercaprol (BAL) and penicillamine with remission of symptoms and normalization of blood pressure after 2 months. This case has relevance for current practice reflecting similarity between mercury intoxication and hypertension secondary to pheochromocytoma.
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PMID:[Arterial hypertension due to mercury intoxication with clinico-laboratorial syndrome simulating pheochromocytoma]. 873 21

Effects of pH on internalization, membrane-binding and efflux of Cd were investigated in LLC-PK1 cells and these effects were compared with those of inorganic mercury (Hg). The cells cultured on monolayers were incubated for 30 min in phosphate buffer at pH 5.5, 6.4 or 7.4 containing 1 microM Cd or Hg. After the incubation, the cells were washed with phosphate buffered saline (PBS) or PBS containing chelating agent (EGTA or BAL) to remove membrane-bound Cd or Hg. The decrease in pH significantly decreased Cd concentration in the cells washed with PBS and with PBS-EGTA, and apparently increased the efflux of Cd from the cells. Similar changes were found in Hg concentration in the cells washed with PBS-BAL and Hg efflux from the cells, but these changes in Hg were less significant than those in Cd, respectively. The decrease in pH-increased Hg concentration in the cells washed with PBS, unlike that of Cd. These results suggest that a decrease in pH decreases the internalized Cd as a result of the decrease in membrane-bound Cd and the increase in Cd efflux. The decrease in pH also appears to decrease the internalized Hg by increasing Hg efflux and to increase the membrane-bound Hg.
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PMID:Comparative studies of cadmium and mercury accumulation by LLC-PK1 cells: effects of pH on uptake and efflux. 891 14

The purpose of this study was to investigate the mechanism of inorganic mercury (Hg) uptake in LLC-PK1 cells, a renal tubular epithelial cell line, and to compare the results with those reported previously by us in rat renal cortical epithelial (RCE) cells in primary culture. The LLC-PK1 cells were cultured for 3-12 days, incubated with 1 microM HgCl2 in Hanks' balanced salt solution at 4 or 37 degrees C for 30 min, and washed with phosphate-buffered saline containing BAL to remove the cell membrane-bound Hg. The uptake of Hg was higher in nonconfluent cultures than in confluent cultures and higher at 37 than at 4 degrees C. In confluent culture (Day 8) Hg uptake at 4 degrees C was only 27% of that at 37 degrees C. The initial accumulation of Hg (5 min) from different concentrations of HgCl2 (0.5-50 microM) was linear and did not show a tendency toward saturation, suggesting that a carrier-mediated process was not involved. Pretreatment of cells with 10 microM FCCP, a metabolic inhibitor and a proton ionophore, 0.5 mm DIDS, an anion transport inhibitor, or 0.5 mM ouabain, a Na+/K+-ATPase inhibitor, resulted in 72, 60, and 57% reduction in Hg uptake, respectively. Furthermore, replacement of 137 mm NaCl in the incubation medium with 137 mM KCl or LiCl or 274 mM mannitol caused 30, 45, and 87% reduction in Hg uptake, respectively. These results suggest that in LLC-PK1 cells, as in RCE cells, Hg uptake is inversely related to cell density and is influenced by membrane fluidity, membrane potential, and HCO3-/Cl- transporter.
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PMID:Mercury uptake by LLC-PK1 cells: dependence on temperature and membrane potential. 934 97

Ca2+ is involved in the regulation of a variety of physiological processes, but a persistent increase in free cytosolic Ca2+ concentrations may contribute to cell injury. Dimercaprol (BAL) is a compound used in the treatment of mercury intoxication, but presents low therapeutic efficacy. The molecular mechanism responsible for the BAL toxicity is poorly known. In the present study, the effect of BAL and inorganic and organic mercury on Ca2+ transport by Ca2+-ATPases located in the sarco/endoplasmic reticulum of fast-skeletal muscle and brain was examined. Ca2+ uptake by brain and fast-skeletal muscle microsomes was inhibited in a dose-dependent manner by Hg2+. The calculated IC50 for Ca2+ uptake inhibition by HgCl2 was 1.05+/-0.09 microM (n = 8) for brain and 0.72+/-0.06 microM (n = 9) for muscle. The difference was significant at p < 0.01 (data expressed as mean +/- SD). At a low concentration (1 microM), 2,3-dimer-captopropanol had no effect on Ca2+ uptake by brain or muscle vesicles and did not abolish the inhibition caused by Hg2+. A high concentration of BAL (1 mM) nearly abolished the inhibition caused by 1.75 microM HgCl2 or 6 microM CH3HgCl in skeletal muscle. Surprisingly, at intermediate concentrations (40-100 microM) BAL partially inhibited Ca2+ transport in brain but had no effect on muscle. Furthermore, ATP hydrolysis by brain or muscle microsomes was not inhibited by BAL. These results suggest that in brain microsomes BAL affects in a different way Ca2+ transport and ATP hydrolysis. The increase in BAL concentration observed after toxic administration of this compound to experimental animals may contribute to deregulate Ca2+ homoeostasis and, consequently, to the neurotoxicity of BAL.
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PMID:2,3-Dimercaptopropanol inhibits Ca2+ transport in microsomes from brain but not from fast-skeletal muscle. 1149 49

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

The present study investigates the possible effects of Hg2+, Pb2+, and Cd2+ on [3H]-glutamate binding. To better understand the role of the thiol-disulfide status on the toxicity of such metals toward glutamatergic neurotransmission, we used three thiol chelating agents, 2,3-dimercaptopropanol (BAL), 2,3-dimercaptopropane 1-sulfonate (DMPS), and meso-2,3-dimercaptosuccinic acid (DMSA). Dithiotreitol (DTT) was tested for its ability to prevent metals-induced inhibition on [3H]-glutamate binding. Hg2+, Pb2+, and Cd2+ showed a concentration-dependent inhibition on [3H]-glutamate binding, and mercury was the most effective inhibitor. BAL did not prevent [3H]-glutamate binding inhibition by Hg2+, Cd2+, and Pb2+. However, DMPS and DMSA prevented the inhibition caused by Cd2+ and Pb2+, but not by Hg2+. DTT did not prevent the inhibition on [3H]-glutamate binding caused by 10 microM Hg2+. In contrast, it was able to partially prevent [3H]-glutamate binding inhibition caused by 40 microM Pb2+ and Cd2+. These results demonstrated that the heavy metals present an inhibitory effect on [3H]-glutamate binding. In addition, BAL was less effective to protect [3H]-glutamate binding inhibition caused by these metals than other chelating agents studied.
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PMID:Interaction between metals and chelating agents affects glutamate binding on brain synaptic membranes. 1464 28

A 17-year-old boy was admitted to hospital because of severe hypertension (200/130 mmHg), headache, irritability, sweating, etc. Initial biochemical tests suggested pheochromocytoma, being treated with nifedipina, clonidina and propranolol. On reporting exposure to mercury vapour, he underwent twenty-four-hour urine screening and measurement of blood mercury which confirmed intoxication. The patient received courses of chelation therapy with dimercaprol (BAL) and penicillamine with remission of symptoms and normalisation of hypertension after 2 months. This case is relevant to current practice regarding similarity between mercury intoxication and hypertension secondary to pheochromocytoma.
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PMID:[Arterial hypertension due to mercury intoxication with clinical and laboratorial syndrome simulating pheochromocytoma]. 1468 74


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