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)

1. We report two cases of acute mercury vapour intoxication in humans. The mercury vapour was released from smelting alloys (gold-mercury amalgam). The alloy was apparently contaminated with an unknown amount of mercury. 2. Within half an hour of the incident, the victims began having moderate headache, nausea, lumbar pain and shortness of breath at rest. The patients were treated with BAL (2,3 dimercaptopropanol), followed by DMSA (2,3 dimercaptosuccinic acid). 3. Serial measurements of mercury metal in plasma and in urine were made for ten days. 4. The results suggest that in spite of the treatment, relatively high concentrations of mercury remain in the plasma for a very long time, and this could be explained by the progressive release of mercury from red blood cells and tissues after oxidation. However, BAL and DMSA did not seem to be the most efficient antidotes. They reduce the plasma inorganic mercury uptake at concentrations of < 50 micrograms I-1.
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PMID:Elemental mercury vapour toxicity: treatment and levels in plasma and urine. 771 4

Factors affecting the renal uptake of inorganic mercury were investigated using primary cultures of rat renal cortical epithelial (RCE) cells under protein- and amino acid-free conditions. The cells were isolated from kidneys of adult rats and cultured. Confluence of culture (cell density), monitored morphologically and by total protein content, was achieved on Day 5. The RCE cells were incubated with 1 microM Hg at 37 degrees C for 30 min, followed by washing with phosphate-buffered saline containing various chelating agents (i.e., EGTA, PEN, DMSA, and BAL) to remove the surface-bound, noninternalized Hg. A substantial portion of Hg was bound to the cell surface. The removal of Hg from these binding sites was dependent on the stability constants of the chelating agents for Hg and lipophilic BAL removed the most Hg. Hg accumulation by the cells was dependent on cell density and decreased as the cell culture became confluent, possibly due to the formation of tight junctions resulting in a majority of the Hg transport occurring through the apical membrane. As measured after BAL washing, metabolic inhibitors, NaF, DNP, and ouabain decreased Hg accumulation by 28% and low temperature (4 degrees C) decreased it by 62%. Dependence of Hg uptake on metabolic energy and temperature suggests that a part of Hg is transported via active transport system. The pronounced decrease of Hg uptake at 4 degrees C indicates that, in addition to active transport, Hg transport also involves simple diffusion, some of which is dependent on membrane fluidity. It is concluded that Hg transport in RCE cells through the apical membrane occurs mainly by diffusion, and to a smaller extent by active transport.
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PMID:Mercury uptake by primary cultures of rat renal cortical epithelial cells. I. Effects of cell density, temperature, and metabolic inhibitors. 774 83

The efficacy of three chelating agents, BAL, DMPS and DMSA has been evaluated in rabbits as treatments for systemic dichloro(2-chlorovinyl)arsine [lewisite] poisoning by the percutaneous route. Chelating agent treatment reduced the incidence and severity of pathological liver changes following lewisite poisoning. There was no marked difference between the three chelating agents for protection against lethality when screened at an equimolar dose of 40 mumol kg-1. The results indicated DMPS and DMSA may prolong survival time compared with BAL. The low toxicity of DMPS and DMSA compared to BAL enabled doses of 160 mumol kg-1 on a more prolonged dosing schedule to be used for DMPS and DMSA. This schedule showed DMPS and DMSA to give a significant improvement in protection against the lethal effects of percutaneous lewisite compared to that of BAL. It was concluded that DMPS and DMSA have significant advantages over BAL for use as treatment for systemic lewisite poisoning.
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PMID:Efficacy of dimercapto chelating agents for the treatment of poisoning by percutaneously applied dichloro(2-chlorovinyl)arsine in rabbits. 810 Apr 35

Gluconeogenesis is one of the metabolic pathways severely affected in acute arsenic poisoning. We have studied gluconeogenesis in isolated kidney tubules of male Sprague-Dawley rats to screen various sulfur compounds for antidotal properties against inorganic and organic arsenicals. Freshly prepared kidney cells from starved rats synthesized glucose from added pyruvate (10 mmol/liter) at a rate of 9.74 +/- 0.90 nmol/min/mg protein (mean +/- SD; n = 61). Gluconeogenesis was inhibited almost 90% in the presence of phenylarsonate (700 mumol/liter), arsenate (350 mumol/liter), arsenite (30 mumol/liter), or PhAsO (1 mumol/liter). mumol/liter). With effective antidotes the rate of gluconeogenesis was restored to almost control values within 10 min. Among 21 sulfur compounds tested, only BAL, DMPS, and DMSA were effective in PhAsO poisoning. With inorganic arsenic also DTE and DTT restored the rate of glucose formation. The observed in vitro efficacies were in good agreement with in vivo results obtained with male NMRI mice severely poisoned with arsenite (As2O3, 20 mg/kg approximately 0.2 mmol As/kg) or PhAsO (3.4 mg/kg approximately 0.02 mmol As/kg). We conclude that isolated kidney tubules are a useful in vitro screening system (a) to compare the metabolic toxicity of various arsenicals and (b) to evaluate potential antidotes.
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PMID:Isolated rat kidney tubules as a screening system for arsenic antidotes. 839 18

More than 4 percent of preschool-aged children in the United States have blood lead levels above 10 microg per dL (0.50 pmol per L), and these levels have been associated with a decline in IQ. The Centers for Disease Control and Prevention advocates the use of a screening questionnaire to identify lead exposure or toxicity in all children. Primary prevention through the removal of lead from gasoline and paint has led to a reduction of blood lead levels in children. Secondary prevention through paint hazard remediation is effective in homes that have a high lead burden. Children with lead levels of 45 to 69 microg per dL (2.15 to 3.35 pmol per L) should receive chelation therapy using succimer (DMSA) or edetate calcium disodium (CaNa2EDTA). Use of both CaNa2EDTA and dimercaprol (BAL in oil) is indicated in children with blood lead levels higher than 70 microg per dL (3.40 micromol per L). Current treatment recommendations are based on the reduction of blood lead levels, which may not represent a significant overall reduction of the lead burden. Clinical trials of existing agents are needed to determine patient-oriented outcomes, such as the effect on IQ.
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PMID:Lightening the lead load in children. 1152 57

The therapeutic use of BAL (2,3-dimercaptopropanol) as treatment for poisoning has been halted by data suggesting serious neurotoxicity. This article is a report on the effects of BAL and other dithiols, DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercaptopropane-1-sulfonic acid), on [3H]glutamate release and uptake by rat brain synaptosomes and [3H]glutamate uptake by synaptic vesicles. BAL (100 microM) inhibited glutamate uptake (30%) and stimulated its basal release (30%) in synaptosomes, without affecting K+-stimulated release. BAL also inhibited glutamate uptake by synaptic vesicles (up to 60%). DMPS and DMSA (100 microM) had no significant effects on these parameters. The data reported here provide some evidence of glutamate involvement in BAL-induced neurotoxicity by demonstrating direct effects of BAL on glutamatergic system modulation.
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PMID:BAL modulates glutamate transport in synaptosomes and synaptic vesicles from rat brain. 1123 55

2,3-Dimercaptopropanol (BAL- British Anti-Lewesite) is a dithiol chelating agent used for the treatment of heavy metal poisoning, however, BAL can produce neurotoxic effects in a variety of situations. Based on the low therapeutic efficiency of BAL other dithiols were developed and DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercaptopropane-1-sulfonic acid) are becoming used for treatments of humans exposed to heavy metals. In the present investigation the effect of dithiols in the glutamatergic system was examined. The results showed that BAL inhibited [3H]MK-801 and [3H]glutamate binding in a concentration-dependent manner. At 100 microM BAL and DMSA caused a significantly inhibition of [3H]MK-801 binding to brain membranes (p < 0.05 by Duncan's multiple range test). BAL at 100 microM caused an inhibition of 40% on [3H]glutamate binding. DMPS and DMSA had no significant effect on [3H]glutamate binding. Dithiotreitol (DTT), abolished the inhibitory effect of BAL on [3H]MK-801 binding. The protection exerted by DTT suggests that BAL inhibit [3H]MK-801 binding by interacting with cysteinyl residues that are important for redox modulation of receptor responses. ZnCl2 inhibited [3H]glutamate and [3H]MK-801 binding to brain synaptic membrane; nevertheless, the inhibitory effect was slight more accentuated for [3H]MK-801 than [3H]glutamate binding (p < 0.05). The inhibition caused by 10 microM ZnCl2 on [3H]MK-801 binding was attenuated by BAL. The findings present in this study may provide the evidence that BAL affect the glutamatergic system and these effects can contributed to explain, at least in part, why BAL, in contrast to DMPS and DMSA is neurotoxic.
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PMID:Effect of dithiol chelating agents on [3H]MK-801 and [3H]glutamate binding to synaptic plasma membranes. 1188 82

Arsenic poisoning was diagnosed in a 26-year-old man who had been criminally intoxicated over the last two weeks preceding admission by the surreptitious oral administration of probably 10 g of arsenic trioxide (As2O3). The patient developed severe manifestations of toxic hepatitis and pancreatitis, and thereafter neurological disorders, respiratory distress, acute renal failure, and cardiovascular disturbances. In addition to supportive therapy, extrarenal elimination techniques and chelating agents were used. Dimercaprol (BAL) and dimercaptosuccinic acid (DMSA or succimer) were used simultaneously as arsenic chelating agents for two days, and thereafter DMSA was used alone. DMSA was administered by intravenous (20 mg/kg/d for five days, then 10 mg/kg/d for six days) and intraperitoneal route. Intravenous DMSA infusion was well tolerated and resulted in an increase in arsenic blood concentration immediately after the infusion. Continuous venovenous hemofiltration combined with hemodialysis, and peritoneal dialysis were proposed to enhance arsenic elimination. It was calculated that over an 11-day period 14.5 mg arsenic were eliminated by the urine, 26.7 mg by hemodialysis, 17.8 mg by peritoneal dialysis, and 7.8 mg by continuous venovenous hemofiltration. These amounts appeared negligible with regard to the probable ingested dose. The patient died on day 26 from the consequences of multiple organ failure, with subarachnoid hemorrhage and generalized infection caused by Aspergillus fumigatus.
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PMID:Acute arsenic poisoning treated by intravenous dimercaptosuccinic acid (DMSA) and combined extrarenal epuration techniques. 1264 60

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

A case of a 27-year-old woman who ingested 9000 mg arsenic trioxide (As2O3) is reported. Classical symptoms of an acute arsenicum (As) poisoning such as gastrointestinal cramps, vomiting, diarrhea, ECG changes and disturbed liver function tests were observed. The absorption of the ingested As was minimalized by a continuous gastric irrigation with highly concentrated NaHCO3 and intestinal cleansing with NaHCO3 and polyethyleneglycol was performed. Forced diuresis, BAL (2,3-dimercaptopropanol) and DMSA (meso-2,3-dimercaptosuccinic acid) were started and therapy to enhance the formation of methylated As derivatives, which are potentially less toxic and which can be excreted more easily, was then administered. The patient survived this massive dose of ingested inorganic As with only polyneuropathy one year later.
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PMID:Survival after a lethal dose of arsenic trioxide. 1553 28


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