Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inorganic arsenic is embryotoxic and teratogenic in chicks, golden hamsters, mice, and rats. Certain dithiol chelators have been reported to protect against arsenite-induced lethality and to decrease arsenic body burden. The present study evaluated the influence of BAL (2,3-dimercapto-1-propanol) and DMPS (sodium 2,3-dimercapto-1-propanesulfonic acid), a water-soluble analogue of BAL, on arsenic-induced embryotoxic and teratogenic effects in the mouse. A series of four BAL or DMPS injections was administered sc to pregnant mice immediately after a single ip injection of 12 mg/kg of sodium arsenite given on Day 9 of gestation and at 24, 48, and 72 hr thereafter. Controls received sc corn oil with or without arsenite. Amelioration by BAL and DMPS of arsenite developmental toxicity was assessed at 15, 30, and 60 mg/kg/day, and 75, 150, and 300 mg/kg/day, respectively. BAL given following arsenite was not able to ameliorate the developmentally toxic effects of arsenite seen in mice, whereas treatment with DMPS at 150 and 300 mg/kg showed significant protective effects against arsenite embryotoxicity and teratogenicity. DMPS administration at 300 mg/kg also protected the dams against arsenite-induced maternal toxicity.
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PMID:Amelioration by BAL (2,3-dimercapto-1-propanol) and DMPS (sodium 2,3-dimercapto-1-propanesulfonic acid) of arsenite developmental toxicity in mice. 137 32

Water soluble analogs of British Anti-Lewisite that are active orally and less toxic than BAL are now available. These agents are 2,3-dimercapto-1-propanesulfonic acid and meso-dimercaptosuccinic acid. Evidence for their effectiveness in preventing the lethal effects of sodium arsenite in mice and lewisite in rabbits is presented. These analogs can be expected to replace BAL in the treatment of heavy metal poisoning.
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PMID:Biological chelation: 2,3-dimercapto-propanesulfonic acid and meso-dimercaptosuccinic acid. 628 18

Meso-dimercaptosuccinic acid (DMSA) and the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS) are analogous in chemical structure to dimercaprol (BAL, British Anti-Lewisite). Dimercaprol was among the first therapeutically useful metal chelating agents and was developed originally as an anti-lewisite agent. Either DMSA or DMPS protects rabbits from the lethal systemic action of dichloro(2-chlorovinyl)arsine (29.7 mumols/kg, also known as lewisite. The analogs are active in this respect when given either sc or po. The stability of each of the three dimercapto compounds in distilled H2O, pH 7.0 at 24 degrees, has been examined for seven days. DMSA retained 82% of its mercapto groups, but no titratable mercapto groups remained in the DMPS or BAL solutions. At pH 5.0, however, there was no striking difference in the stability of the three dimercapto compounds (78-87%) over a seven day period. DMSA and DMPS warrant further investigation as water soluble metal binding agents in both in vivo and in vitro experiments.
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PMID:Anti-lewisite activity and stability of meso-dimercaptosuccinic acid and 2,3-dimercapto-1-propanesulfonic acid. 629 30

meso-Dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propanesulfonic acid, Na salt (DMPS), and N-(2,3- dimercaptopropyl )- phthalamidic acid (DMPA) are water soluble analogs of 2,3-dimercapto-1-propanol (BAL). The relative effectiveness or therapeutic index of these dimercapto compounds in protecting mice from the lethal effects of an LD99 of sodium arsenite is DMSA greater than DMPS greater than DMPA greater than BAL in the magnitude of 42:14:4:1, respectively. DMPS, DMPA, or DMSA will mobilize tissue arsenic. BAL, however, increases the arsenic content of the brain of rabbits injected with sodium arsenite. These results raise the question as to the appropriateness of BAL as the treatment for systemic arsenic poisoning. Either DMSA or DMPS, when given sc or po, will protect rabbits against the lethal systemic effects of subcutaneously administered Lewisite . DMPS and DMSA have promise as prophylactics for the prevention of the vesicant action of Lewisite . The sodium arsenite inhibition of the pyruvate dehydrogenase (PDH) complex can be prevented and reversed in vitro or in vivo by DMPS, DMSA, DMPA, or BAL. Of them all, DMPS is most potent and BAL appears to be the least potent. The usefulness of all these dimercapto compounds would be enhanced by a careful study of their metabolism and biotransformation. These dimercapto compounds are in a great many respects orphan drugs. At this stage of their development, it is very difficult for the clinician to obtain funds to study them clinically even though they appear to be useful for treatment of poisoning by any one of the heavy metals.
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PMID:DMSA, DMPS, and DMPA--as arsenic antidotes. 632 46

The 74As content of the brain of rabbits was doubled following administration of BAL (2,3-dimercapto-1-propanol). DMPS (2,3-dimercapto-1-propanesulfonic acid, sodium salt), however, decreased the rabbit brain arsenic concentration. The use of BAL as the drug of choice for treatment of arsenic intoxication should be viewed with caution and re-examined.
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PMID:BAL increases the arsenic-74 content of rabbit brain. 661 33

Cadmium was preferentially bound to metallothionein in tissues 24 h after CdCl2 injection. Of a number of chelating agents examined, only 2,3-dimercapto-1-propanol (BAL) was effective in mobilizing Cd from metallothionein into bile. Structurally similar dithiols such as 1,3-dimercaptopropanol and 2,3-dimercapto-1-propanesulfonic acid were not effective. Diethylenetriamine pentaacetic acid increased only the urinary excretion of Cd. Biliary excretion of Cd increased with increasing dose of BAL, and there was a concurrent decrease in hepatic Cd levels without any increase in renal concentration. BAL was effective even 14 d after Cd injection. The form of Cd excreted in the bile after BAL injection in chronic exposure has not yet been characterized. Initial studies suggested that it was not metallothionein but was a low-molecular-weight Cd complex, probably with BAL.
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PMID:Biliary excretion of cadmium in rat. VI. Mobilization of cadmium from metallothionein by 2,3-dimercaptopropanol. 739

The common earthworm (Lumbricus terrestris) is being evaluated in our laboratories as a substitute for mice in metal toxicity studies. These two disparate species have enzymes in common, such as catalase, superoxide dismutase and glutathione-S-transferase. Also, worms respond similarly to these rodents for selenium and nickel toxicity. Worms are less sensitive, however, to metal toxicity. In this study earthworms were challenged with three different arsenic compounds: arsenite, arsenate and the vesicant phenyldichloroarsine (PDA). The median lethal dose for each arsenic compound was determined. The order of toxicity of the arsenic compounds to the worms was PDA > arsenite > arsenate (24 h LD50 values were 189.5, 191.0 and 519.4 mumol kg-1, respectively). Individual mammalian dithiol antidotes, namely the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS), meso-dimercaptosuccinic acid (DMSA) or 2,3-dimercapto-1-propanol (BAL), were injected into the worms 5 min after various doses of the arsenic compound were administered. The decreases in acute toxicity values were recorded. All three antidotes protected the worms against arsenic toxicity with varying degrees of effectiveness. The protective action for the inorganic arsenic compounds was in the order DMPS > DMSA > BAL. For the organic arsenical, PDA, the most effective antidote was BAL.
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PMID:Evaluation of three antidotes on arsenic toxicity in the common earthworm (Lumbricus terrestris). 752 93

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

Diesel exhaust particles (DEP) contain quinones that are capable of catalyzing the generation of reactive oxygen species in biological systems, resulting in induction of oxidative stress. In the present study, we explored sulfhydryl oxidation by phenanthraquinone, a component of DEP, using thiol compounds and protein preparations. Phenanthraquinone reacted readily with dithiol compounds such as dithiothreitol (DTT), 2,3-dimercapto-1-propanol (BAL), and 2,3-dimercapto-1-propanesulfonic acid (DMPS), resulting in modification of the thiol groups, whereas minimal reactivities of this quinone with monothiol compounds such as GSH, 2-mercaptoethanol, and N-acetyl-L-cysteine were seen. The modification of DTT dithiol caused by phenanthraquinone proceeded under anaerobic conditions but was accelerated by molecular oxygen. Phenanthraquinone was also capable of modifying thiol groups in pulmonary microsomes from rats and total membrane preparation isolated from bovine aortic endothelial cells (BAEC), but not bovine serum albumin (BSA), which has a Cys34 as a reactive monothiol group. A comparison of the thiol alkylating agent N-ethylmaleimide (NEM) with that of phenanthraquinone indicates that the two mechanisms of thiol modification are distinct. Studies revealed that thiyl radical intermediates and reactive oxygen species were generated during interaction of phenanthraquinone with DTT. From these findings, it is suggested that phenanthraquinone-mediated destruction of protein sulfhydryls appears to involve the oxidation of presumably proximal thiols and the reduction of molecular oxygen.
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PMID:Oxidation of proximal protein sulfhydryls by phenanthraquinone, a component of diesel exhaust particles. 1195 33