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  • 1
    Digitale Medien
    Digitale Medien
    Melatonin reduces oxidative stress and increases gene expression in the cerebral cortex and cerebellum of aluminum-exposed rats (2005)
    Oxford, UK : Munksgaard International Publishers
    Journal of pineal research 39 (2005), S. 0 
    Details
    ISSN: 1600-079X
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract:  The pro-oxidant activity of aluminum (Al), the protective role of exogenous melatonin, as well as the mRNA levels of some antioxidant enzymes, were determined in cortex and cerebellum of rats following exposure to Al and/or melatonin. Two groups of male rats received intraperitoneal injections of Al lactate or melatonin at doses of 7 mg Al/kg/day and 10 mg/kg/day, respectively, for 11 wk. A third group of animals received concurrently Al lactate (7 mg Al/kg/day) plus melatonin (10 mg/kg/day) during the same period. A fourth group of rats was used as control. At the end of the treatment, the cerebral cortex and cerebellum were removed and processed to examine the following oxidative stress markers: glutathione transferase (GST), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase, glutathione peroxidase (GPx), catalase (CAT), thiobarbituric acid reactive substances (TBARS), as well as protein content. Moreover, gene expression of Cu-ZnSOD, MnSOD, GPx and CAT was evaluated by real-time RT-PCR. On the other hand, Al, Fe, Mn, Cu and Zn concentrations were determined in cortex and cerebellum of rats. Oxidative stress was promoted in both neural regions following Al administration, resulting from the pro-oxidant activity related with an increase in tissue Al concentrations. In contrast, melatonin exerted an antioxidant action which was related with an increase in the mRNA levels of the antioxidant enzymes evaluated. The results of the present investigation emphasize the potential use of melatonin as a supplement in the therapy of neurological disorders in which oxidative stress is involved.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1600-079X.2005.00225.x
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  • 2
    Digitale Medien
    Digitale Medien
    Effects of Some Chelating Agents on Urinary Copper Excretion by the Rat (1995)
    s.l. : American Chemical Society
    Chemical research in toxicology 8 (1995), S. 942-948 
    Details
    ISSN: 1520-5010
    Quelle: ACS Legacy Archives
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1021/tx00049a007
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  • 3
    Digitale Medien
    Digitale Medien
    Control of some aspects of cis-platinum nephrotoxicity (1986)
    Springer
    Archives of toxicology 59 (1986), S. 167-171 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Cis-platinum ; Walker 256 carcinoma ; Nephrotoxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The elevations of blood urea nitrogen and serum creatinine caused by cis-platinum in rats can be prevented by a combination of procedures centered around the administration of sodium N-methyl-N-dithiocarboxyglucamine (NaG), before and very soon after the cis-platinum is administered in hypertonic (4.5%) saline. Elevations inblood urea nitrogen and serum creatinine levels subsequent to such treatment are largely eliminated. These same procedures appear to have no effect on the anti-tumor action of the cis-platinum, as measured by tumor size and mass and by survival times, in female Sprague-Dawley rats inoculated with the Walker 256 carcinoma. The degree of myelosuppression, as measured by the white blood cell count is also slightly reduced. White blood cell counts returned to normal values more rapidly in animals treated with NaG than in those treated with cis-platinum alone. An examination of the dose-response curve for the suppression of cis-platinum nephrotoxicity by NaG shows that this can be achieved with mole ratios of NaG: cis-platinum as low as 1∶1 given after appropriate pretreatment. A preliminary structure-activity study on the suppression of cis-platinum induced elevations in blood urea nitrogen and serum creatinine by four closely related dithiocarbamates shows that this can also be achieved effectively by several dithiocarbamates in which the nitrogen atom bears polar substituents.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00316327
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  • 4
    Digitale Medien
    Digitale Medien
    Relative efficacy of chelating agents as antidotes for acute gallium nitrate intoxication (1987)
    Springer
    Archives of toxicology 59 (1987), S. 382-383 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Gallium nitrate ; Deferoxamine mesylate ; Citric acid ; Succinic acid ; Malic acid ; Oxalic acid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Twelve chelating agents were administered to mice by IP injection to compare their relative effectiveness in preventing death after a single IP injection of gallium nitrate. Na2Ca-ethylenediaminetetraacetate (EDTA), Na3Ca-diethylenetriaminepentaacetate (DTPA), dimercaptosuccinic acid (DMSA), 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron), sodium diethyldithiocarbamate (DDC), L-cysteine and sodium salicylate were not effective for acute gallium nitrate intoxication. The therapeutic indices of the effective chelators were: 25.4 (deferoxamine mesylate), 35.7 (citric acid), 42.3 (succinic acid), 52.2 (malic acid) and 111.1 (oxalic acid).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00295095
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  • 5
    Digitale Medien
    Digitale Medien
    Antidotes for zinc intoxication in mice (1988)
    Springer
    Archives of toxicology 61 (1988), S. 321-323 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Zinc ; Mice ; Intraperitoneal administration ; Zinc antidotes ; EDTA ; DTPA ; CDTA ; d-penicilamine ; DMPS ; DMSA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Sixteen chelating agents were examined to determine their relative efficacy as antidotes in acute zinc acetate intoxication in mice after i.p. administration. For a i. p. dose of 0.49 mmol/kg (LD50) of zinc acetate, the i. p. administration of chelating agents at a 2∶1 and 5∶1 mole ratio resulted in a significant antidotal action for EDTA, DTPA, CDTA, d-penicillamine (d-PA), DMPS and DMSA. EGTA, l-cysteine, triethylentetraamine (TTHA), N-acetylcysteine (NAC), 4,5-dihydroxi-1,3-benzenedisulfonic acid (Tiron), sodium salicylate, glutathione, sodium diethyldithiocarbamate (DDC), 6-mercaptopurine and N-acetyl-d, l-penicillamine (NAPA) were not effective for acute zinc acetate poisoning. The therapeutic indices and therapeutic effectiveness of the most effective chelators were, respectively: EDTA (5.0, 7.0), DTPA (7.3, 13.7), CDTA (8.6, 6.3), d-PA (4.6, 1.9), DMPS (1.3, 1.0), DMSA (3.2, 5.4). DTPA, CDTA, and EDTA appear to be the most effective agents of those tested in offsetting acute zinc intoxication in mice.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00364857
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  • 6
    Digitale Medien
    Digitale Medien
    Developmental toxicity evaluation of gallium nitrate in mice (1992)
    Springer
    Archives of toxicology 66 (1992), S. 188-192 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Developmental toxicity ; Gallium nitrate ; Mice
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Gallium nitrate, a drug with antitumor activity, is presently undergoing clinical trials as a chemotherapeutic agent for the treatment of certain malignancies. Since there are very limited published animal toxicity data available, this study was conducted to investigate the potential adverse developmental effects of this drug. Pregnant Swiss mice were administered intraperitoneally gallium nitrate at 12.5, 25, 50, and 100 mg/kg/day on days 6, 8, 10, 12, and 14 of gestation. Monitors for maternal toxicity were body weight, food consumption and clinical signs. At sacrifice (day 18) maternal weight, liver and kidney weights, and gravid uterine weights were measured. Gestational parameters monitored were numbers of total implants, resorptions, postimplantation losses, and dead fetuses. Live fetuses were sexed, weighed, and examined for external, internal and skeletal malformations and variations. Maternal toxicity was noted in all the gallium nitrate-treated groups. Embryo/fetal toxicity was evidenced by a decrease in the number of viable implants, a reduction in fetal weight, and an increase in the number of skeletal variations (12.5, 25, 50 and 100 mg/kg). No significant increase in the incidence of malformations was observed at 12.5, 25, or 50 mg/kg. The no-observable-adverse-effect level (NOAEL) for both maternal and developmental toxicity of gallium nitrate was 〈12.5 mg/kg.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01974013
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  • 7
    Digitale Medien
    Digitale Medien
    Evaluation of the effects of chelation therapy with time following strontium exposure to mice (1991)
    Springer
    Archives of environmental contamination and toxicology 21 (1991), S. 612-620 
    Details
    ISSN: 1432-0703
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Energietechnik , Medizin
    Notizen: Abstract The effect of increasing the time interval between strontium exposure and chelation therapy was studied in male Swiss mice. Diethylenetriaminepentaacetic acid (DTPA), ethyleneglycol-bis(β-amino-ethylether)-N,N′-tetraacetic acid (EGTA), 4,7,13,16,21,24-hexaoxa-1,10-diazabycyclo[8.8.8]-hexacosane (Kryptofix® 222), tartaric acid, and 1,13-bis(8-chinolyl)-1,4,7,10,13-pentaoxatridecan (Kryptofix® 5) were administered intraperitoneally at 0, 6, 12, and 24 h after subcutaneous injection of 1,139 mg/kg of strontium nitrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of strontium into urine and feces was determined for five days after which time the animals were killed, and the concentration of strontium was determined in various tissues. Only Kryptofix 222 was capable of increasing the total urinary elimination of strontium when given immediately after strontium exposure, whereas the amount of total strontium excreted into the feces was significantly enhanced by treatment with EGTA at 0 or 24 h after strontium injection, or with Kryptofix 222 at 6 h after strontium exposure. However, Kryptofix 222, tartaric acid, and Kryptofix 5 reduced the concentration of strontium in bone at 0, 6, or 12 h after strontium injection, whereas at 24 h only Kryptofix 5 significantly lowered the concentration of the metal in bone. The results of this study indicate that the length of time before initiating chelation therapy for strontium removal may influence remarkably the effectiveness of this therapy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01183885
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  • 8
    Digitale Medien
    Digitale Medien
    Assessment of the developmental toxicity of deferoxamine in mice (1995)
    Springer
    Archives of toxicology 69 (1995), S. 467-471 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Key words: Maternal toxicity ; Developmental toxicity ; Deferoxamine ; Mice
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Deferoxamine (DFO), an efficient chelating agent available for the treatment of iron and aluminium overload, was evaluated for developmental toxicity in Swiss mice. Intraperitoneal injections of DFO were given to pregnant animals at 0, 44, 88, 176, and 352  mg/kg per day on gestational days 6 through 15. Maternal clinical status was monitored daily during and after treatment. Fetal parameters, including external, visceral, and skeletal malformations and variations, were assessed. Mice were killed on day 18. No maternal mortality was observed, but dams exhibited reduced body weight gain during treatment at 88, 176, and 352 mg/kg per day. Body weight at termination, corrected body weight, and food consumption were reduced in all groups. In contrast, the only significant treatment-related embryo/fetal effect was a decrease in the number of live fetuses per litter at 352 mg/kg per day. The no-observable-adverse-effect level (NOAEL) for maternal toxicity of DFO was 〈44 mg/kg per day, whereas the NOAEL for developmental toxicity was 176 mg/kg per day. In summary, intraperitoneal administration of DFO to mice during organogenesis produced developmental toxicity in the presence of maternal toxicity. Because of the remarkable maternal toxicity of DFO, extreme caution in the use of this drug is recommended during pregnancy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002040050200
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  • 9
    Digitale Medien
    Digitale Medien
    Comparison of the effectiveness of several chelators after single administration on the toxicity, excretion and distribution of cobalt (1986)
    Springer
    Archives of toxicology 58 (1986), S. 278-281 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Cobalt ; Intraperitoneal administration ; Mice ; EDTA ; DTPA ; DMSA ; N-Acetylcysteine ; Glutathione ; L-Cysteine ; D,L-penicillamine ; BAL
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of the chelating agents Na2Ca-ethylendiaminetetraacetate (EDTA), Na3Ca-diethylentriaminepentaacetate (DTPA), L-cysteine, 2,3-dimercaptosuccinic acid (DMSA), N-acetyl-L-cysteine (NAC), glutathione, D,L-penicillamine (D,L-PEN) and 2,3-dimercaptopropanol (BAL) on the toxicity, distribution and excretion of intraperitoneally injected cobalt were studied in male Swiss mice. To determine the effect of the various chelators on the toxicity of cobalt, various doses of CoCl2 (0.60–1.80 mmol/kg) were given, followed immediately by the IP administration of the chelator (at a dose equal to one-fourth of their respective LD50). EDTA and DTPA were the most effective. EDTA, DTPA and L-cysteine, NAC and glutathione were also the most effective in increasing the urinary excretion of cobalt and reducing the concentration of the metal in various tissues. EDTA appears to be the most effective agent of those tested in the prevention of acute cobalt intoxication.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00297121
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  • 10
    Digitale Medien
    Digitale Medien
    Treatment of acute lead intoxication. A quantitative comparison of a number of chelating agents (1990)
    Springer
    Archives of environmental contamination and toxicology 19 (1990), S. 185-189 
    Details
    ISSN: 1432-0703
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Energietechnik , Medizin
    Notizen: Abstract The efficacy of several chelating agents in alleviating acute lead intoxication has been investigated in male Swiss mice. The relative effectiveness of diethyl-enetriaminepentaacetic acid (DTPA), ethyleneglycolbis-(β-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 ethylenediamine-tetraacetic 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01056085
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