COMPARATIVE ALUMINUM MOBILIZING ACTIONS OF SEVERAL CHELATORS IN ALUMINUM-LOADED UREMIC RATS

被引:23
作者
GOMEZ, M
DOMINGO, JL
DELCASTILLO, D
LLOBET, JM
CORBELLA, J
机构
[1] ROVIRA & VIRGILI UNIV,SCH MED,TOXICOL & BIOCHEM LAB,E-43201 REUS,SPAIN
[2] UNIV BARCELONA,SCH MED,DEPT TOXICOL,E-08036 BARCELONA,SPAIN
[3] ROVIRA & VIRGILI UNIV,SCH MED,SURG UNIT,E-43201 REUS,SPAIN
来源
HUMAN & EXPERIMENTAL TOXICOLOGY | 1994年 / 13卷 / 02期
关键词
D O I
10.1177/096032719401300213
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The relative effectiveness of deferoxamine (DFO), 1,2-dimethyl-1,3-hydroxypyrid-4-one (L1), and citric and succinic acids in mobilizing and promoting excretion of aluminium (Al) were compared in female uraemic rats which had previously received aluminium nitrate nonahydrate i.p. in a daily dose of 45 mg kg(-1) for 3 weeks (5 days/week), Chelators were administered s.c. at doses equal to one-eighth of their respective ID50 for five days. L1 was also given p.o. in doses of 200 mg kg(-1) day(-1), Total urines were collected 24 h after each chelator administration, Total urinary Al excreted over the 5-day period, expressed as mg kg(-1), were: controls, 3.4: DFO-treated, 4.5 (P<0.05); citric acid-treated, 3.7; and succinic acid-treated, 2.7, Although the daily amounts of Al excreted into urine by L1-treated rats were significantly higher (P<0.001) than those of the controls, most animals died during the period of treatment. Measurements of Al in selected tissues 24 h after the last administration of each chelator revealed that none of the compounds significantly altered the Al concentration in bone, kidney, and brain, whereas only DFO and succinic acid significantly reduced the levels of Al in spleen, Moreover, L1 (given s.c. or p.o.) and citric acid treatment led to a significant reduction in the liver Al burden. These results indicate the need for further investigations to determine the toxicity and the therapeutical safety margins of L1.
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收藏
页码:135 / 139
页数:5
相关论文
共 39 条
  • [1] DIALYSIS ENCEPHALOPATHY SYNDROME - POSSIBLE ALUMINUM INTOXICATION
    ALFREY, AC
    LEGENDRE, GR
    KAEHNY, WD
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1976, 294 (04) : 184 - 188
  • [2] ALFREY AC, 1984, B NEW YORK ACAD MED, V60, P210
  • [3] ALFREY AC, 1980, AM J CLIN NUTR, V33, P109
  • [4] ALFREY AC, 1986, KIDNEY INT, V29, P853
  • [5] DEFEROXAMINE INCREASES THE SUSCEPTIBILITY OF BETA-THALASSEMIC, IRON-OVERLOADED MICE TO INFECTION WITH LISTERIA-MONOCYTOGENES
    AMPEL, NM
    BEJARANO, GC
    SAAVEDRA, M
    [J]. LIFE SCIENCES, 1992, 50 (18) : 1327 - 1332
  • [6] CATSCH A, 1979, CHELATION HEAVY META
  • [7] DAVIES SC, 1983, LANCET, V2, P181
  • [8] EFFECT OF ASCORBIC-ACID ON GASTROINTESTINAL ALUMINUM ABSORPTION
    DOMINGO, JL
    GOMEZ, M
    LLOBET, JM
    RICHART, C
    [J]. LANCET, 1991, 338 (8780) : 1467 - 1467
  • [9] INFLUENCE OF SOME DIETARY CONSTITUENTS ON ALUMINUM ABSORPTION AND RETENTION IN RATS
    DOMINGO, JL
    GOMEZ, M
    LLOBET, JM
    CORBELLA, J
    [J]. KIDNEY INTERNATIONAL, 1991, 39 (04) : 598 - 601
  • [10] COMPARATIVE EFFECTS OF SEVERAL CHELATING-AGENTS ON THE TOXICITY, DISTRIBUTION AND EXCRETION OF ALUMINUM
    DOMINGO, JL
    GOMEZ, M
    LLOBET, JM
    CORBELLA, J
    [J]. HUMAN TOXICOLOGY, 1988, 7 (03): : 259 - 262