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PubMed1989

Effects of selected chelating agents on organ distribution and excretion of manganese after inhalation exposure to 54MnCl2. I. Injection of chelating agents.

The effect of 1,2-cyclohexylene-aminotetraacetic acid (CDTA), diethylenetriaminepentaacetis acid (DTPA) and 2,3-dimercaptol-1-propanesulphonic acid, sodium salt (DMPS) on Mn distribution and excretion in rats was examined after 1 hr exposure to 54MnCl2 (approximately 0.1 microgram Mn/m3). All complexing agents were injected i.p., 0.32 mM/kg/day, for 7 days, starting either immediately after exposure (day 0, group I), or 1 week after exposure (day 7, group II). The controls were injected i.p. with 4 ml/kg of 0.9% saline. Activity of 54Mn was determined in lung, liver, kidney, and brain, 24 hrs after the last treatment and in urine and feces collected for 24 hrs on days 1-7 and 8-14 respectively. CDTA and DTPA administered immediately after Mn exposure appeared to be most effective, resulting in a two-fold decrease of 54Mn in brain and kidney, and a statistically significant decrease in lung (DTPA) and liver (CDTA). In group II a two-fold decrease of 54Mn in kidney and liver was observed with CDTA. There was also a decrease after DTPA administration. DMPS was not effective in these experiments. On the first day after exposure, 54Mn levels in urine were more than 15 and 25 times higher for CDTA and DTPA, respectively than for saline, in the early treatment group. Excretion of Mn in feces was not affected. Our data show that the effectiveness of removing inhaled Mn depends both on the complexing agent and the time of its administration.

Animals↗
PubMed1980

[Enhancement of 67Ga tumor-to-blood ratios by chelating agent (author's transl)].

Chelating agent, such as CaEDTA, CaDTPA, D-penicillamine, DMSA, desferoxamine, NTA, cysteine ethyl ester, BAL, alpha-MPG, phthalein complexone, were tested as a possible contrast enhancing agent for tumor imaging with 67Ga-citrate. The intravenous administration of a chelating agent to Ehrlich's tumor bearing mice, one hour after the injection of 67Ga-citrate, accelerated the blood clearance with only a very slight change of activity in the target, increasing the tumor-to-blood ratio, and consequently achieving a better visualization. Among the tested chelating agents, D-penicillamine showed the highest target-to-nontarget ratio at a shorter time: a good tumor-to-blood ratio, performed after 24 hr with non-treated animals, was achieved in only 1-3 hr with post-treated animals. Thus, D-penicillamine hold a considerable promise as a contrast enhancing agent for future clinical use.

Animals↗
PubMed1975

Studies on the stability of injectable solutions of some phenothiazines. Part 2: Effect of chelating agents and antioxidants.

Chelating agents (disodium EDTA, DTPA, HEDTA and NTA) exhibit a stabilizing action towards phenothiazines to different extents. This could be correlated to the stability constants of their metal chelates as well as to the dependency of these constants on the pH-value of the solution. Antioxidants (sodium bisulphite, sodium dithionite, and sodium metabisulphite) also exert a stabilizing effect which could be correlated--in the first place--to the pH-value of the solution. The sulphur content of the antioxidant might also be relevant to such an effect.

Antioxidants↗
PubMed1976

The excretion and distribution of inorganic mercury in the rat as influenced by several chelating agents.

Among 15 chelating agents tested, sodium-2,3-dimercaptopropane 1 sulfonate (DMPS), 2,3-dimercaptopropanol (BAL), sodium-mercaptoethyliminodiacetate (MEIDA), and D-penicillamine (PA) exerted an influence on the excretion of Hg and its distribution in the organs. The excretion pattern however, is different for these compounds, and, from the practical point of view, a favourable effect is exhibited only by DMPS which enhances the urinary excretion rate and lowers the Hg-concentration in all organs.

Animals↗
PubMed1997

Biodegradabilities of ethylenediamine-N,N'-disuccinic acid (EDDS) and other chelating agents.

Biodegradabilities of chelating agents were tested with activated sludge. Ethylenediaminetetraacetic acid (EDTA) remained intact in the effluent even after acclimation for 100 days, but propanediamine-N,N'-disuccinic acid (PDDS) and nitrilotriacetic acid (NTA) were biodegraded after acclimation for 5 and 23 days, respectively. Optical isomers of ethylenediamine-N,N'-disuccinic acid (EDDS) had different biodegradabilities: SS- and RS-isomers were susceptible to biodegradation, but the RR-isomer was resistant. SS-isomer was degraded even by activated sludge without acclimation.

Biodegradation, Environmental↗
PubMed1983

Inhibition of microsomal oxidation of alcohols and of hydroxyl-radical-scavenging agents by the iron-chelating agent desferrioxamine.

Rat liver microsomes (microsomal fractions) catalyse the oxidation of straight-chain aliphatic alcohols and of hydroxyl-radical-scavenging agents during NADPH-dependent electron transfer. The iron-chelating agent desferrioxamine, which blocks the generation of hydroxyl radicals in other systems, was found to inhibit the following microsomal reactions: production of formaldehyde from either dimethyl sulphoxide or 2-methylpropan-2-ol (t-butylalcohol); generation of ethylene from 4-oxothiomethylbutyric acid; release of 14CO2 from [I-14C]benzoate; production of acetaldehyde from ethanol or butanal (butyraldehyde) from butan-1-ol. Desferrioxamine also blocked the increase in the oxidation of all these substrates produced by the addition of iron-EDTA to the microsomes. Desferrioxamine had no effect on a typical mixed-function-oxidase activity, the N-demethylation of aminopyrine, nor on the peroxidatic activity of catalase/H2O2 with ethanol. H2O2 appears to be the precursor of the oxidizing radical responsible for the oxidation of the alcohols and the other hydroxyl-radical scavengers. Chelation of microsomal iron by desferrioxamine most likely decreases the generation of hydroxyl radicals, which results in an inhibition of the oxidation of the alcohols and the hydroxyl-radical scavengers. Whereas desferrioxamine inhibited the oxidation of 2-methylpropan-2-ol, dimethyl sulphoxide, 4-oxothiomethylbutyrate and benzoate by more than 90%, the oxidation of ethanol and butanol could not be decreased by more than 45-60%. Higher concentrations of desferrioxamine were required to block the metabolism of the primary alcohols than to inhibit the metabolism of the other substrates. The desferrioxamine-insensitive rate of oxidation of ethanol was not inhibited by competitive hydroxyl-radical scavengers. These results suggest that primary alcohols may be oxidized by two pathways in microsomes, one dependent on the interaction of the alcohols with hydroxyl radicals (desferrioxamine-sensitive), the other which appears to be independent of these radicals (desferrioxamine-insensitive).

Alcohols↗
PubMed1990

[Chelating agents].

The problem of chelating agents used as antidotes in intoxications with metals is intensively studied during the past 20 years. Due to the complex nature of the action of these substances in the organism their investigation is a typically interdisciplinary problem. The submitted review gives the theoretical background of the formation of chelate in the organism, the strategy of research of new substances is discussed and findings on the main groups of chelating agents used in human medicine are summarized.

Animals↗
PubMed1989

Chelating agents and rat liver mitochondria.

The chelating agents (EGTA and EDTA) and inorganic phosphate (Pi) are the most variable components of experiments involving isolated liver mitochondria. In the absence of EGTA or EDTA, swelling induced by Pi leads to rapid loss of endogenous adenine nucleotides to adenosine. Chelating agents prevent swelling and loss of adenine nucleotides. Concentrations below about 0.1 mM are ineffective. The protective effects depend on the continuous presence of the chelating agent; they are lost on washing EGTA-containing suspensions with chelating-agent-free medium. We question the accepted view that chelating agents stabilize mitochondria by binding Ca2+ to prevent activation of phospholipase.

Adenine Nucleotides↗
PubMed2004

Heavy metal stabilization in municipal solid waste incineration flyash using heavy metal chelating agents.

Heavy metal chemical stabilization with synthesized heavy metal chelating agent was assessed for flyash from municipal solid waste incinerator. Flyash can contain heavy metals (e.g. Pb, Cd) which can leach. A new kind of heavy metal chelating agent showed more attractive competition than inorganic chemicals in stabilizing flyash. The synthesizing method of this kind of heavy metal chelating agent was explained in this paper, and the technology process and treatment efficiency of the chelating agent in treating flyash were experimentally studied, which was compared with the results of inorganic chemical agents such as sodium sulfide and lime. The heavy metals in flyash were stabilized more effectively by using heavy metal chelating agents than by using sodium sulfide and lime, furthermore, the stabilized products using the chelating agents can meet the landfill disposal controlling standards for heavy metal waste. pH-dependent leaching experiment showed the stabilized flyash by treatment with heavy metal chelating agent could keep long-term stabilization within a broad range of pH value. Thus, the risk of secondary pollution for the stabilized products was reduced dramatically when the environment condition changes during its disposal period.

Carbon↗
PubMed1996

The use of chelating agents in occupational lead poisoning.

Chelating agents have long been used in the pharmacological treatment of lead poisoning, whose management is still a problem, particularly in developing countries. This article reviews the pharmacological properties of dimercaprole, peniclliamine. CaNa2EDTA and dimercaprosuccinic acid, examines their indications, contraindications and side effects and discusses the possible use of each drug in occupational Pb poisoning. Proposals are also presented for the treatment and follow-up of subjects with signs and symptoms of poisoning and of subjects with low-moderate Pb absorption. CaNa2EDTA seems to be the most reliable and safer chelating agent nowadays available and with a wider spectrum of action. DMSA seems to be promising in the treatment of occupational Pb poisoning. Even though there is no doubt that chelation therapy has significantly contributed to reduce mortality and morbidity from occupational Pb poisoning, the efficacy of this treatment in subjects with subtle neurological or renal damage has not yet been studied properly.

Body Burden↗
PubMed2004

Evaluation of chelating agents as anti-angiogenic therapy through copper chelation.

The evaluation of several sets of polyamine donor chelating agents including a selection of novel hexadentate 1,3,5-cis,cis-triaminocyclohexane (tach) based derivatives were performed in an in vitro endothelial cell proliferation assay to assess their cytotoxicity and selectivity as novel anti-angiogenic agents. The selective nature of the anti-angiogenic agents for human umbilical vein endothelial cells (HUVEC) was compared to a normal fibroblast cell line and a human Glioma cell line to evaluate these compounds. Linear tri- and tetra-polyamines were superior to both macrocyclic and the tach based polyamine chelating agents in terms of selectivity of its inhibitory activity toward the proliferation of HUVEC cells compared to the fibroblast and human Glioma cells. The linear polyamine, triethylenetetramine (22), previously reported to possess anti-angiogenic properties failed to demonstrate any selectivity for inhibiting the proliferation of HUVEC cells compared to the fibroblast and human Glioma cells.

Angiogenesis Inhibitors↗
PubMed1974

Effect of chelating agents on the susceptibility of some strains of gram-negative bacteria to some antibacterial agents.

The effects of ethylenediaminetetraacetic acid and related chelating agents on the susceptibility of Pseudomonas aeruginosa and other strains of gram-negative bacteria to some beta-lactam antibiotics and some non-antibiotic antibacterial agents have been studied by two methods: (i) the determination of minimal inhibitory concentrations in the presence and absence of a chelating agent; and (ii) pretreatment with a chelating agent, followed by exposure for up to 120 min at 37 C to a beta-lactam drug in a nutrient medium or to the other type of antibacterial agent in a non-nutrient environment. The pretreatment technique gave the more significant results, especially with chlorhexidine, cetrimide, and benzalkonium chloride. Chelating agents that had previously been found to give a low order of activity as measured by effects on bacterial viability nevertheless appeared to induce some changes in the surface layers of the treated organisms, rendering them susceptible to sub-inhibitory concentrations of non-antibiotic drugs.

Anti-Bacterial Agents↗
PubMed1996

Inhibition of Trypanosoma cruzi epimastigotes in vitro by iron chelating agents.

The relative effectiveness of 20 iron chelating agents in suppressing the growth and multiplication of Trypanosoma cruzi epimastigotes has been examined in vitro. 1,2-Dimethyl-3-hydroxypyrid-4-one (L1) and several of its newly synthesised N-substituted analogs containing hydrophobic substituents were significantly more effective than deferoxamine, even though they possess only two donor sites for iron(III) while deferoxamine has six. Analogs with hydrophilic substituents were uniformly less active than L1 itself. Variations in effectiveness as the polarity of the compound is varied indicate that the ability to cross the cellular membrane is of critical importance in the determination of the in vitro trypanocidal activity of iron(III) chelating agents. A group of four tris(2-aminoethyl)amine based tris-imines were also screened, all of which had poor activity (0-28% inhibition). Among the other iron(III) chelating agents which showed a relatively high level of activity at 50 and 100 micrograms/ml were salicylhydroxamic acid (70 and 73% inhibition) and hydroxyurea (42 and 52% inhibition). N,N'-Di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid and acetohydroxamic acid exhibited only slight activity at 50 and 100 micrograms/ml. The best of these iron(III) chelating agents were as effective against the epimastigote form at both 50 and 100 micrograms/ml (74-82% inhibition) as benznidazole (81% inhibition), the drug currently used in the clinic.

Animals↗
PubMedDate not supplied

Treatment of acute lead intoxication. A quantitative comparison of a number of chelating agents.

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.

Animals↗
PubMed1996

Preparation and protein conjugation of a divinyl sulphone derivatized bifunctional chelating agent.

A new bifunctional chelating agent with a novel linking arm, 2-[p-¿N-benzyl-N-(2-vinylsulfoethyl)¿- (aminobenzyl)¿-1,3-propane-diamine-N,N,N',N'-tetraacetic acid (VS-PDTA) was synthesized and was conjugated to protein for the purpose of attaching radiometals to monoclonal antibodies (MAbs). The effect of various parameters such as ligand concentration, protein concentration, pH, temperature and reaction period on the conjugation have been examined using chromatographic (SE and TLC) analysis after labeling with 111In. The parameters and chemical variables studied have significant effects on the efficiency and rate of protein conjugation.

Chelating Agents↗