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)

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

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

The cadmium mobilizing properties of two newly synthesized esters of meso-2,3-dimercaptosuccinic acid in mice have been examined. They are: di(2'-methoxyethyl) meso-2,3-dimercaptosuccinate ([-CH(SH)COOCH2CH2OR]2, R = CH3; MEDMS), and di(2'-ethoxyethyl) meso-2,3-dimercaptosuccinate ([-CH(SH)COOCH2CH2OR]2, R = CH2CH3; EEDMS), conveniently prepared from dimercaptosuccinate acid with 2-methoxyethanol and 2-ethoxyethanol, respectively. Mobilization studies in mice of aged in vivo cadmium deposits using five ip injections of 0.40 mmol/kg of each chelator in peanut oil clearly indicate that both compounds, MEDMS and EEDMS, are significantly superior to 2,3-dimercaptopropan-1-ol (BAL) in depleting the whole body burden of cadmium. The reductions caused by MEDMS and EEDMS were approximately 20 and 26%, respectively, whereas under similar dosage regimens BAL effected about only a 12% reduction. The esters were neither equal nor superior to BAL for the reduction of renal cadmium levels, MEDMS being the least effective. For the mobilization of hepatic cadmium deposits, both were quite promising (MEDMS, 20%; EEDMS, 34% reduction) compared to BAL (only 2% reduction). There was no accumulation of cadmium with either MEDMS or EEDMS in any of the other organs examined--spleen, testes, pancreas, and particularly the brain. These compounds enhance the fecal excretion of cadmium by a factor of 25- to 40-fold but have very little effect on the urinary excretion of this element. The present study reveals that the order of overall efficacy is EEDMS greater than MEDMS greater than BAL, considering the liver and whole body burdens of cadmium, but BAL greater than EEDMS greater than MEDMS in terms of the efficacy in reducing cadmium levels in the kidneys.
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PMID:The mobilization of intracellular cadmium by alkoxyethyl esters of meso-2,3-dimercaptosuccinic acid. 217 57

The efficacy of several chelating agents in alleviating acute lead intoxication has been investigated in male Swiss mice. The relative effectiveness of diethylenetriaminepentaacetic acid (DTPA), ethyleneglycolbis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA), cyclohexanediaminetetraacetic acid (CDTA), L-cysteine, N-acetyl-L-cysteine (NAC), ascorbic acid, sodium diethyldithiocarbamate (DDC), 2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercapto-1-propanesulfonate (DMPS) in reducing lethality of lead was examined. Significant increases in survival were noted with CDTA, ascorbic acid, DMSA, and DMPS. Therapeutic effectiveness (TEF) was determined for these compounds; TEF for ethylenediaminetetraacetic acid (EDTA) and for 2,3-dimercaptopropanol (BAL) was also determined; CDTA (2.33) and EDTA (1.73) showed the highest values. In subsequent experiments, the effect of the chelating agents on the distribution and excretion of lead was investigated. Lead acetate trihydrate was administered subcutaneously at doses of 37.8 mmol/kg (LD50), and fifteen minutes later, chelators were given intraperitoneally at doses approximately equal to one-fourth of their respective LD50 values. EDTA, DTPA and CDTA were the most effective agents in increasing the urinary excretion of lead, whereas DTPA, CDTA, and DDC increased significantly the fecal excretion of lead. EDTA, DDC, and CDTA were the most effective chelators in reducing the concentration of lead found in various tissues. On the basis of these results, CDTA may be considered as an alternative in the treatment of acute lead poisoning.
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PMID:Treatment of acute lead intoxication. A quantitative comparison of a number of chelating agents. 232 19

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

An examination was made of the relative efficacies of 2,3-dimercapto-1-propanol (BAL) and three diesters ( [CH(SH)COOR]2; DMDMS, R = CH3; DEDMS, R = C2H5; and Di-PDMS, R = CH(CH3)2] of meso-2,3-dimercaptosuccinic acid (DMSA) in mobilizing freshly injected lead from mice. These diesters, like BAL, reduced the lead levels resulting from freshly injected lead in both the soft tissues (liver, kidneys, spleen, and brain) and the bone (tibia). After treatment with the dimethyl (DMDMS), the diethyl (DEDMS), and the diisopropyl (Di-PDMS) esters the lead content of each of the organs was significantly less than that present in the untreated controls. Each of the diesters reduced lead levels in the kidneys, liver, and spleen significantly below those levels found after BAL treatment. The action of the diesters in reducing brain lead levels was comparable to that of BAL. Di-PDMS was the most effective of these compounds and was significantly superior to BAL. Each of the esters was also significantly more effective than BAL in reducing the whole body level of lead.
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PMID:Mobilization of lead by esters of meso-2,3-dimercaptosuccinic acid. 254 77

2,3-Dimercaptosuccinic acid (DMSA) is a new orally active heavy metal chelator for the treatment of childhood Pb intoxication on an outpatient basis. The influence of DMSA, as well as other chelating agents, on gastrointestinal 203Pb absorption and whole-body 203Pb retention was examined. Groups of Sprague-Dawley rats (230-260 g) were gavaged with a solution containing approximately 25 mg/kg Pb [as Pb(NO3)2] plus 15 microCi 203Pb. Some groups were then immediately given 0.11 mmol/kg of either DMSA, CaNa2EDTA, D-penicillamine, or BAL by oral gavage, while other groups received the same drugs by ip injection. Control groups received solutions of the drug vehicles po or ip. Whole-body Pb retention and gastrointestinal Pb absorption (whole body retention + urinary Pb excretion) were significantly decreased in rats that received DMSA po. This finding implies that the use of DMSA to treat childhood lead intoxication on an outpatient basis is not associated with a risk for increased Pb absorption.
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PMID:Influence of 2,3-dimercaptosuccinic acid on gastrointestinal lead absorption and whole-body lead retention. 255 28

The dimethyl, diethyl, di-n-propyl, diisopropyl (Di-PDMS), and di-n-butyl esters of meso-2,3-dimercaptosuccinic acid were prepared by esterification of the parent acid and were subsequently purified and characterized. Their relative ability to mobilize cadmium from its aged (greater than 30 days) deposits was evaluated in mice in comparison with 2,3-dimercapto-1-propanol (BAL). All but the dimethyl ester were superior to BAL in reducing the hepatic cadmium levels, though none was superior in reducing renal cadmium levels. Their efficacy in reducing hepatic cadmium levels had the result that all except the dimethyl ester were significantly more effective than BAL in reducing total cadmium body burdens in mice. The most effective of these compounds, Di-PDMS, caused a reduction of whole body cadmium of 59% (i.e., to 41% of control values) under conditions where the corresponding reduction found for BAL was only 18% (i.e., to 82% of control value). The predominant route of excretion of cadmium subsequent to administration of these compounds is via the fecal route (greater than 99%). A synergistic effect was found in the reduction of whole body and kidney cadmium burdens when Di-PDMS was used in combination with trisodium calcium diethylenethriaminepentaacetate.
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PMID:Esters of meso-dimercaptosuccinic acid as cadmium-mobilizing agents. 284 65

The effects of the chelating agents Na2Ca-ethylendiaminetetraacetate (EDTA), Na3Ca-diethylentriaminepentaacetate (DTPA), L-cysteine, 2,3-dimercaptosuccinic acid (DMSA), N-acetyl-L-cysteine (NAC), glutathione, D,L-penicillamine (D,L-PEN) and 2,3-dimercaptopropanol (BAL) on the toxicity, distribution and excretion of intraperitoneally injected cobalt were studied in male Swiss mice. To determine the effect of the various chelators on the toxicity of cobalt, various doses of CoCl2 (0.60-1.80 mmol/kg) were given, followed immediately by the IP administration of the chelator (at a dose equal to one-fourth of their respective LD50). EDTA and DTPA were the most effective. EDTA, DTPA and L-cysteine, NAC and glutathione were also the most effective in increasing the urinary excretion of cobalt and reducing the concentration of the metal in various tissues. EDTA appears to be the most effective agent of those tested in the prevention of acute cobalt intoxication.
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PMID:Comparison of the effectiveness of several chelators after single administration on the toxicity, excretion and distribution of cobalt. 308 29

The relative abilities of approximately 20 chelating agents to act as antagonists for acute and chronic lead poisoning have been examined in the mouse. The acute LD50 for lead acetate trihydrate was determined and found to be 135.3 mg Pb/kg for i.p. injection with a 95% confidence interval of 87.1-210.3 mg Pb/kg. The relative efficacy of chelating agents to reduce liver, kidney, spleen, bone and brain levels of lead was determined. The movement of lead from the liver to the bone was followed during the first 7 days post injection and was found to result in appreciable changes in the lead levels of these organs from day to day during this entire period. Of the compounds examined, the ones which were most effective in mobilizing lead under various conditions included meso-2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercaptopropane-1-sulfonate (DPMS), disodium calcium ethylene-diaminetetraacetate (Na2CaEDTA), trisodium zinc triethylenetetraminehexa-acetate, dicalcium ethylenediaminetetra(methylenephosphonate) (Ca2EDTPO) and diethyl dimercaptosuccinate (DEMSA) and 2,3-dimercapto-1-propanol (BAL).
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PMID:Comparative mobilization of lead by chelating agents. 321 88


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