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 effect of two vicinal dithiols, 2,3-dimercaptopropan-1-ol (BAL) and N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA), and a dithiocarbamate, sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate (MeOBGDTC), on the biliary excretion of cadmium was examined in rats. Tissue cadmium levels were also determined following the measurements of biliary excretion of cadmium. At 30 min after the injection of CdCl2.2.5H2O (1 mg/kg, iv) each rat was given 400 mumol/kg ip of one of the compounds, BAL, DMPA or MeOBGDTC. While all the compounds increased the biliary excretion of cadmium, the most effective was MeOBGDTC, whose administration resulted in a 580% increase in biliary cadmium content. The effectiveness of the MeOBGDTC may be due to the presence of both nonpolar and nonionizing polar groups attached to nitrogen. MeOBGDTC was able to mobilize cadmium to the bile even after the occurrence of the synthesis of metallothionein and the incorporation of the cadmium into it. An attempt was also made to determine the chemical nature of the Cd-MeOBGDTC complex present in the bile by comparing a newly synthesized authentic sample of Cd(MeOBGDTC)2 complex with the hot dioxane extract of the freeze-dried bile samples using thin-layer chromatography and proton NMR. The results suggested that cadmium excreted in the bile in part, is complexed to MeOBGDTC and glutathione.
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PMID:A comparative study of the influence of vicinal dithiols and a dithiocarbamate on the biliary excretion of cadmium in rat. 189 71

The consequences of the mobilization of aged intracellular cadmium from its in vivo deposits in mice by chelating agents were examined. The chelating agents used were BAL, sodium N-benzyl-D-glucamine dithiocarbamate (NaB), Diisopropyl meso-2,3-dimercaptosuccinate(Di-PDMS) and sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate(4-Me0), all previously shown capable of causing statistically significant decreases in either renal or hepatic cadmium burdens in rodents. They were given at a level of 400 mumol/kg (i.p.) daily for 10 days to mice previously loaded with a total of 10 mg CdCl2.2.5 H2O/kg. Under these conditions a significant decrease in the renal cadmium level occurred following treatment with BAL, NaB, and 4-MeO; hepatic cadmium levels decreased significantly following treatment with NaB and 4-MeO. Pathological examination of the kidneys, liver, and testes in these animals showed that chelate mobilization of the cadmium produced no noticeable changes in the histopathology of these organs in comparison with that observed for the animals which had been given only cadmium and had undergone no chelate treatment. The results suggest that the mobilization of such aged cadmium from in vivo deposits need not result in any deleterious changes in the kidneys, liver or testes.
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PMID:Intracellular cadmium mobilization sequelae. 231 52

Diethyl dimercaptosuccinate (DEDMS) was prepared and found to be capable of mobilizing cadmium from mice one month after they had been given an injection (i.p.) of 0.03 mg CdCl2.2.5H2O containing 1.0 microCi of 109 CdCl2. When pure, DEDMS is a waxy solid with a melting point of 61-62 degrees C which is soluble in warm peanut oil. Its LD50 value (i.p.) in mice is approximately 2.6 mmol/kg, a value which allows it to be given at a higher dosage than other known lipid-soluble dithiols. This compound is especially effective in reducing hepatic and whole body levels of cadmium; it is not as effective as 2,3-dimercaptopropanol (BAL) in reducing renal cadmium levels.
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PMID:Mobilization of aged in vivo cadmium deposits by diethyl dimercaptosuccinate. 283 77

The effects of several mono-, di-, and trithiols (400 mumol/kg) in mobilizing Cd from metallothionein were studied in rats 24 h after a single injection of 109CdCl2 (1 mg kg/Cd). BAL (2,3-dimercaptopropanol) and propanetrithiol (1,2,3-trimercaptopropane) were the most effective mercaptans in increasing the biliary excretion of Cd (3.1 and 5.5% of administered dose, respectively, compared to 0.04% in control injected with propylene glycol) in in situ experiments with a significant decrease in hepatic Cd. Propane-1-thiol was inactive and propanetrithiol was the most toxic of the compounds studied. A number of propane dithiols having sulfhydryl groups at different carbon positions with and without substituents (OH or SO-3) and dimercaptoethane were also tested for effectiveness in removing Cd. All the lipophilic compounds with two adjacent sulhydryl groups were effective in increasing the biliary excretion of Cd, but were less effective than BAL and propanetrithiol. The major form of Cd in liver cytosols of rats pretreated with CdCl2 and injected with mercaptans was metallothionein. A small amount of Cd in liver cytosol and a major portion of biliary Cd in propanetrithiol-injected rats were bound to high-molecular-weight proteins when fractionated on Sephadex G-75 columns. On the other hand, after injection of BAL, most of the Cd in the bile was associated with a fraction of molecular weight 10,000. Even though Cd was present mainly as metallothionein in livers of Cd-pretreated rats, the biliary forms of Cd after injection of BAL and propanetrithiol were different. Similar results were obtained when Cd was added in vitro to bile samples collected from control rats that were injected with these chelating agents alone. However, the Sephadex G-75 elution profile of Cd-BAL and Cd-propanetrithiol after direct addition to control rat bile showed Cd complexes of identical molecular weight (less than 6000). These results suggested that the Cd-binding ligands present in bile after injection of BAL and propanetrithiol were different from and had a higher molecular weight than the complexes in vitro with Cd and the respective chelating agents.
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PMID:Biliary excretion of cadmium in rat. V. Effects of structurally related mercaptans on chelation of cadmium from metallothionein. 709 93

The rate of Cd accumulation by adult rat liver parenchymal cells in serum free primary culture in the presence of 100 microM CdCl2 was 10 times greater than that by non-parenchymal Kupffer cells. Addition of the monothiol chelating agents, cysteine and penicillamine, decreased Cd uptake in both cell types, the effect becoming more pronounced as the monothiol concentration was increased from 0.1 to 1.0 mM. These monothiols thus appear to reduce the availability of Cd for transport across the cell membrane. In contrast 1-10 molar excesses of the dithiol agents 2,3-dimercaptopropanol (BAL) or dithiothreitol (DTT) stimulated to variable extents the rate of Cd accumulation 2-10-fold in parenchymal cells and by over 100-fold in Kupffer cells. Supplementation of the media with 3% serum had little effect on the Cd accumulation in the presence of dithiols. Intravenous injection of Cd (0.05 mg/kg DCdCl2) with up to a 10-fold molar excess of cysteine or penicillamine had little effect on the hepatocellular Cd distribution. However Cd uptake by non-parenchymal cells was increased markedly by the simultaneous administration of BAL or DTT in 2 or 10 molar excess. Evidence is provided that these results may be partially explained by the endocytosis, particularly in Kupffer cells, of colloidal complexes of Cd which are formed with the dithiols but not the monothiols. These observations demonstrate that the physicochemical form of Cd determines its hepatocellular distribution which may be an important factor in the manifestation of Cd toxicity after thiol treatment.
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PMID:Effects of thiol agents on the accumulation of cadmium by rat liver parenchymal and Kupffer cells. 729 98

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