Depleted uranium (DU) has been widely applied in industrial and military activities, and is often obtained from producing fuel for nuclear reactors. DU may be released into the environment, polluting air, soil, and water, and is considered to exert both radiological and chemical toxicity. In humans and animals, DU can induce multiple health effects, such as renal tubular necrosis and bone malignancies. This review summarizes the known information on DU's routes of entry, mechanisms of toxicity, and health effects. In addition, we survey the chelating agents used in ameliorating DU toxicity.
Animals ; Chelating Agents ; pharmacology ; Humans ; Inactivation, Metabolic ; Radiation-Protective Agents ; pharmacology ; Uranium ; metabolism ; toxicity

BACKGROUNDAlthough there are several drugs and drug combinations for the treatment of Pneumocystis carinii (P. carinii) pneumonia, all drugs have the toxicity as well as low efficacy. Iron chelators have been proposed as a source of new drugs for combating these infections. We hypothesized that iron chelators would suppress the growth of P. carinii by deprivation of the nutritional iron required for growth. In this study, a short-term axenic culture system of P. carinii was established. Daphnetin (7,8-dihydroxycoumarin), a known iron chelator, was demonstrated to exhibit in vitro activity against P. carinii in this system.

METHODSP. carinii organisms were obtained from the lungs of immunosuppressed rats. The culture system consisted of Iscove Dulbecco Eagle's Minimum Essential Medium (IMDM), supplemented with S-adenosyl-L-methionine, N-acetylglucosamine, putrescine, L-cysteine, L-glutamine, 2-mercaptoethanol, and fetal bovine serum, and was maintained at 37 degrees C, in 5% CO(2), 95% O(2), at the optimal pH of 8.0. The culture system was used to assess the effect of daphnetin on the proliferation of P. carinii organisms. The ultrastructures of the treated organisms were observed by transmission electron microscopy.

RESULTSThe number of cysts and trophozoites increased 8- to 9-fold and 11- to 12-fold, respectively, after 10 days of culture. Daphnetin was found to suppress the growth of P. carinii in a dose-dependent manner at concentrations between 1 micromol/L and 20 micromol/L. The inhibitory activity was suppressed by the chelation of daphnetin with ferrous sulfate in a 2:1 molar ratio, but it was not suppressed by mixing the culture medium with magnesium sulfate. Reduction of P. carinii numbers after treatment with daphnetin correlated with morphological changes in the organisms, as determined by transmission electron microscopy.

CONCLUSIONSDaphnetin can suppress the growth of P. carinii in vitro. The efficacy of daphnetin in suppressing the the growth of P. carinii in vitro is related to its ability to chelate iron.

Iron ; physiology ; Iron Chelating Agents ; pharmacology ; Microscopy, Electron ; Pneumocystis carinii ; drug effects ; growth & development ; ultrastructure ; Umbelliferones ; pharmacology

OBJECTIVETo study the molecular mechanism of apoptosis of leukemic cells (K562 cells) induced by iron chelating agent deferoxamine (DFO).

METHODSThe exponentially growing K562 cells were used (1×10(6)/mL) in this study. The K562 cells were treated with different concentrations of DFO (10, 50 and 100 mmol/L), DFO+FeCl3 (10 μmol/L each) or normal saline (blank control). The cellular labile iron pool was measured with a fluorimetric assay using the metalsensitive probe calcein-AM. The viable count and cell viability were determined by typanblue assay. Cell apoptosis was determined by morphological study and flow cytometry assay. Caspase-3 activity in K562 cells was detected by colorimetry.

RESULTSAfter DFO treatment, the cellular labile iron pool and the viability of K562 cells were reduced and the cell apoptosis increased in a time- and dose-dependent manner compared with the blank control group. The apoptosis rate of K562 cells in the DFO+FeCl3 treatment group was not significantly different from that in the blank control group. The caspase-3 activity in K562 cells increased significantly 24 hrs after 50 and 100 μmmol DFO treatment when compared with the blank control group (P<0.01). There was a negative correlation between cellular labile iron pool and caspase-3 activity of K562 cells (r=-0.894, P<0.05).

CONCLUSIONSDFO induces apoptosis of leukemic cells possibly through decreasing cellular labile iron pool and increasing caspase-3 activity of the cells.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Deferoxamine ; pharmacology ; Flow Cytometry ; Humans ; Iron Chelating Agents ; pharmacology ; K562 Cells

To study the lead excretion effect of the chelator Zn-DTPA on the lead intoxication mice, inductively coupled plasma mass spectrometry (ICP-MS) was applied to detect the lead content of biological samples. The acute lead intoxication mice model was established by injecting lead acetate intraperitoneally with the dose of 1 mg. Zn-DTPA was administered intraperitoneally to mice once daily for five consecutive days 4 h after intoxication. Control group, model group, combination of Zn-DTPA and Ca-DTPA group were evaluated at the same time. The urine was collected every day. The mice were sacrificed in batches in the 2rd, 4th, 6th day. Biological samples including urine, whole blood, femur and brain were prepared and nitrated. Lead concentration was detected by ICP-MS. The result showed that Zn-DTPA could increase lead content in urine markedly and reduce lead content in blood, femur and brain.
Animals ; Chelating Agents ; pharmacology ; Lead ; pharmacokinetics ; urine ; Lead Poisoning ; drug therapy ; Mass Spectrometry ; Mice ; Pentetic Acid ; pharmacology

Serum dopamine-beta-hydroxylase (DBH) inhibition has been reported in lead workers treated with CaNa2EDTA and in alcoholic patients repeatedly treated with the alcohol aversive drug Disulfiram. The mechanism of inhibition involves Cu++ chelation at the active site of DBH. The effect of CaNa2EDTA and Disulfiram on serum DBH has been compared to the effect of dithiocarbamate pesticides in vitro for the possible use of serum DBH determination for the biological monitoring of workers exposed to these pesticides. Most dithiocarbamates inhibit human serum DBH at micromolar concentrations (range of I50, 0.027-1.6 mumol/L). The inhibitory potency increased from methyl- and dimethyl dithiocarbamates to diethyl dithiocarbamates up to the most potent ethylene bisdithiocarbamates. The I50 of CaNa2EDTA was 3.8 mumol/L, higher than those of dithiocarbamates. Copper addition to the test system reactivated at stoichiometric concentrations dithiocarbamate-inhibited DBH indicating that both base line values and percent of inhibition can be calculated in a single blood sample. Results suggest that serum DBH determination could be useful in case of acute poisoning involving high doses of dithiocarbamate pesticides.
Alcohol Deterrents ; pharmacology ; Biomarkers ; blood ; Chelating Agents ; pharmacology ; Disulfiram ; pharmacology ; Ditiocarb ; pharmacology ; Dopamine beta-Hydroxylase ; blood ; drug effects ; Edetic Acid ; pharmacology ; Female ; Humans ; Male ; Pesticides ; blood

FOR smear layer removal from root canal walls, ethylenediaminetetraacetic acid (EDTA) is an effective chelating agent and its efficiency depends upon a lot of factors such as concentration, pH, duration of application, the type of the solution, the root canal length, penetration depth of the material, and hardness of the dentin.The aim of this scanning electron microscopic study was to evaluate the effectiveness of 19% EDTA gel on smear layer removal at different time periods when used as a final step in the irrigation regime.
Chelating Agents ; pharmacology ; Dental Pulp Cavity ; drug effects ; ultrastructure ; Edetic Acid ; pharmacology ; Gels ; Humans ; In Vitro Techniques ; Microscopy, Electron, Scanning ; Root Canal Irrigants ; pharmacology ; Smear Layer ; Therapeutic Irrigation

Animals ; Chelating Agents ; pharmacology ; Lead ; toxicity ; Learning ; drug effects ; Memory Disorders ; drug therapy ; Mice ; Morus ; chemistry ; Plant Extracts ; chemistry ; pharmacology ; Random Allocation ; Succimer ; pharmacology

AIMTo study the effects of sodium magnesium fructose diphosphate (SMFD) on free calcium concentration and nitric oxide synthase activity of ischemic synaptosome, so as to explore the protective mechanisms of SMFD on cerebral ischemia.

METHODSThe synaptosomes from normal rat brain were prepared by phase partition and cultured with oxygen-glucose deprivation to establish ischemic synaptosome model. The intrasynaptosomal free calcium concentration and nitric oxide synthase activity were detected separately after the synaptosomes were co-incubated with SMFD (1.3 mmol.L-1) or fructose-1, 6-diphosphate (FDP, 4.0 mmol.L-1) for 60 min.

RESULTSSMFD decreased the free calcium concentration and reduced the activity of nitric oxide synthase (NOS) of ischemic synaptosomes. Its effects were more powerful than those of FDP.

CONCLUSIONSMFD may protect neurons from ischemic injury by preventing intracellular Ca2+ overload and inhibiting the activity of nitric oxide synthase.

Animals ; Brain Ischemia ; enzymology ; metabolism ; Calcium ; metabolism ; Chelating Agents ; pharmacology ; Fructosediphosphates ; pharmacology ; Magnesium ; chemistry ; Male ; Nitric Oxide Synthase ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Sodium ; chemistry ; Synaptosomes ; metabolism

BACKGROUND: Since metallo-beta-lactamase (MBL)-producing isolates can hydrolyze carbapenem and also easily transfer the resistance genes to other bacteria, a rapid and accurate detection of MBL has become very important. We evaluated the utility of Mueller Hinton agar (MHA) biplate containing dipicolinic acid (DPA) as a screening method to detect IMP-1 and VIM-2 type MBL-producing isolates. METHODS: Based on our preliminary tests using various concentrations of DPA, 200 and 300 microg/mL concentration of DPA were chosen for further study. Bacterial lawns were grown on MHA biplate, one half of which contained DPA while the other did not. The inhibition zone around the imipenem (IPM) disk on both sides of this plate was compared. The stability of DPA in the stored DPA-MHA biplate was also evaluated during three months using two MBL- and one non-MBL-producing isolates. RESULTS: When the criterion of a > or =7 mm increase of inhibition zone around the IPM disk on the MHA containing DPA compared to MHA without DPA was used, the sensitivities and specificities were 94.7% and 97.6% for 200 microg/mL DPA-MHA biplate, and 98.2% and 97.6% for 300 microg/mL DPA-MHA biplate, respectively. The activity of the DPA in this biplate was stable for three months. CONCLUSIONS: Assays using DPA 300-MHA biplate were highly sensitive and specific for the detection of IMP-1 and VIM-2 type MBL-producing bacteria. In addition, it is easy to perform; so, it may be useful to apply this method for detection of IMP-1 and VIM-2 type MBL in clinical laboratories.
Agar ; Anti-Bacterial Agents/*pharmacology ; Bacteriological Techniques ; Chelating Agents/chemistry/*pharmacology ; Drug Resistance, Bacterial ; Gram-Negative Bacteria/drug effects/enzymology/*isolation & purification ; Imipenem/*pharmacology ; Picolinic Acids/chemistry/*pharmacology ; Reagent Kits, Diagnostic ; Sensitivity and Specificity ; beta-Lactamases/*analysis/biosynthesis

AIMTo assess the antioxidative properties and the mechanism of action of dihydromyricetin (DMY) from Ampelopsis grossedentata.

METHODSThe antioxidative properties of DMY were measured by scavenging 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and inhibiting lipid peroxidation induced by FeSO4-edetic acid in linoleic acid. The mechanism of antioxidative properties of DMY was tested by measuring the chelating activities of DMY for Fe2+ with ultraviolet spectrum (UV) method.

RESULTSThe specific absorption of DPPH radical solution at 517 nm was reduced 73.3%-91.5% when DMY was added into the reaction solution in the concentration range from 0.01% to 0.04%. DMY was shown to greatly inhibit the increase of lipid peroxidation (LPO) values in linolei acid system catalyzed by FeSO4-edetic acid. The reaction rates (A532.min-1) of lipid peroxidation were 0.0021-0.0004 in the concentration range from 0.01% to 0.04% and the inhibition activities of DMY was found to be in a concentration-dependent manner. The mechanism of antioxidative properties of DMY was chelating Fe2+ in the Fe(2+)-dependent lipid peroxidation system.

CONCLUSIONDMY showed great antioxidative effect and would be a good natural antioxidant.

Ampelopsis ; chemistry ; Antioxidants ; isolation & purification ; pharmacology ; Chelating Agents ; pharmacology ; Flavonols ; chemistry ; isolation & purification ; pharmacology ; Free Radical Scavengers ; isolation & purification ; pharmacology ; Lipid Peroxidation ; drug effects ; Molecular Structure ; Plants, Medicinal ; chemistry