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 effects of some new chelating agents on the cadmium burden of CHO cells in culture were investigated. The chelators were sodium-N-(4-methoxybenzyl)-D-glucamine-dithiocarbamate (MeOBG-DTC), sodium-N-benzyl-D-glucaminedithiocarbamate (BG-DTC) and diisopropylmeso-2,3-dimercapto succinate (DiP-DMSA). The results were compared with the effect of the well known dimercaptopropanol (BAL). The derivates of dithiocarbamate are much less toxic than DiP-DMSA and BAL. All chelators effectively prevent Cd uptake into the cells. Mobilization of intracellular Cd, however, is more effective by the DTC-derivatives than by DiP-DMSA or BAL. Within the cell the major fraction of Cd after 48 hours incubation is found in the nuclei and cytosol and very little in the peroxisomes. The chelating agents remove the metal mostly from nuclei and cytosol. Incubation of the cells with cadmium leads to the induction of a Cd binding protein of an apparent molecular weight of 12500 Da, presumably metallothionein. MeOBG-DTC is more effective in removing the metal from this protein than BG-DTC.
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PMID:Effects of chelating agents on the cadmium burden of cells in culture. 165 37

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 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

Trapping of an arterial bolus in the kidney by 40 sec aortic occlusion permitted demonstration of diffusion-limited and Zn-sensitive renal uptake of nonfiltered but diffusible Cd from plasma; mercaptoethanol (ME) or 2,3-dimercaptopropanol (BAL) had been added to the bolus to prevent sequestration of the metals by plasma protein. Cadmium taken up by the kidney under these conditions, whether from blood or glomerular filtrate, unlike Zn, did not return to blood over a period of 2-3 min. Nor was Cd thus accumulated removed by EDTA; it had presumably been transferred into cells. The diffusion dependence of this internalization shows it to be a relatively slow process, as it is in jejunum. In contrast, uptake of Cd tightly bound in a lipid-soluble complex with diethyldithiocarbamate (DDTC) is rapid and flow dependent. Slow uptake in the presence of ME and its inhibition by Zn are therefore not likely to involve movement of undissociated ME complex across the cell membranes. Instead, it is suggested that (1) Cd-binding sites on the membrane possess a relatively high affinity for Cd and can compete for it with ME, and (2) it is the resulting Cd-membrane interaction which, as in jejunum, is depressed by Zn. During transient occlusion kidneys could be loaded with up to 25 micrograms Cd/g cortex without evidence of immediate malfunction. Inhibition of amino acid transport, as previously described, is seen only after an initiation period of 1-2 days following CdME injection, although cortical Cd levels at that time have decreased. The finding of a slowly developing inhibition of amino acid carrier systems suggests an indirect action of Cd; by implication, unique threshold concentrations should not be defined for Cd in renal cortex following subchronic exposures without reference to the duration of exposure.
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PMID:Acute cadmium uptake by rabbit kidneys: mechanism and effects. 231 15

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 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 conditioned flavor-aversion paradigm was used to assess the toxicity of acutely administered cadmium and the interaction of cadmium with the heavy-metal chelating agents dimercaprol (BAL) and dimercaptosuccinic acid (DMSA). Shortly after consuming saccharin, rats received ip administration of cadmium either alone or in combination with sc administration of BAL or DMSA. Three days later they were given the choice between consuming saccharin or water, and saccharin preferences were recorded. When compared to rats receiving either nothing or the vehicle, rats receiving cadmium displayed significant reductions in saccharin preference (i.e., conditioned flavor aversions). BAL and DMSA were also capable of producing conditioned flavor aversions when given alone. Rats receiving cadmium in combination with either BAL or DMSA displayed significant, but not complete attenuations of conditioned flavor aversions when compared to the flavor aversions of rats receiving cadmium alone. Chelator-induced blockade of cadmium-induced flavor-aversion conditioning was not obtained when BAL or DMSA administration was delayed by 4 hr. Attenuation of cadmium-induced aversions by BAL and DMSA extends earlier findings of an attenuation of lead-induced flavor-aversion conditioning by these complexing agents, and thus demonstrates further the utility of the flavor-aversion conditioning paradigm in characterizing metal-chelator interactions.
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PMID:Behavioral consequences of chelator administration in acute cadmium toxicity. 285 73

When garlic (Allium sativum) was administered to rat per os simultaneously with cadmium, methylmercury and phenylmercury to detect the protective effect against the heavy metal poisoning, accumulation of heavy metals in liver, kidneys, bone and testes were decreased, and histopathological damages and the inhibition of serum alkaline phosphatase activities by heavy metals were reduced. Such effect of garlic was not shown in the 1.7% garlic treated group and most remarkable in the 6.7% garlic treated group. The protective effect of garlic was superior to those of 2,3 dimercapto-1-propanol (BAL) and D-penicillamine (PEN), and nearly similar to those of 2,3-dimercaptosuccinic acid (DMSA) and N-acetyl-DL-penicillamine (APEN), the current remedies, while garlic was not effective as a curative agent for heavy metal poisoning. The excretion of cadmium was enhanced, more through feces than urine by garlic but the effect to the urinary excretion of cadmium was not significant comparing with DMSA or APEN when cadmium was ip injected in the first 3 days during the 12 days of oral administration of DMSA, APEN or garlic.
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PMID:A study on the effect of garlic to the heavy metal poisoning of rat. 326 78

Sodium N-benzyl-D-glucamine dithiocarbamate (NBG-DTC), which was newly synthesized, 2,3-dimercaptopropanol (BAL), and N-methyl-D-glucamine dithiocarbamate (NMG-DTC) were compared for their relative efficacies in the distribution and excretion of cadmium in rats exposed to cadmium. Rats were injected ip with 109CdCl2 (1 mg Cd and 10 microCi 109Cd/kg) and 3 days later, they were treated with the chelating agents (400 mumol/kg) every other day for 2 weeks. These chelating agents were effective in removing cadmium from the body without increasing the amount of cadmium in the kidney. After treatment with these chelating agents, cadmium was excreted mainly in the feces through the bile and the fecal excretion of cadmium by NBG-DTC was significantly larger than that by BAL or NMG-DTC. The hepatic cadmium content after treatment with NBG-DTC was much more decreased than that with BAL or NMG-DTC. The renal cadmium content was decreased only after treatment with NBG-DTC. These chelating agents did not result in the redistribution of cadmium to brain, testes, and heart. The growth of rats was little retarded by treatment with NBG-DTC and NMG-DTC, but was retarded by treatment with BAL. The treatment with NBG-DTC decreased the tissue amounts of Zn, Fe, and Mn to a small extent as compared with the treatment with cadmium alone. The results of this study reveal that the injection of NBG-DTC to rats pretreated with cadmium can more effectively remove cadmium from the body without the mobilization of cadmium to the kidney, the critical organ in cadmium toxicity, and without redistribution of cadmium to other tissues such as brain, testes, and heart, than injection of BAL and NMG-DTC.
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PMID:Comparative effects of three chelating agents on distribution and excretion of cadmium in rats. 370 73


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