Monensin improves the effectiveness of meso-dimercaptosuccinate when used to treat lead intoxication in rats

被引:24
作者
Hamidinia, SA
Erdahl, WL
Chapman, CJ
Steinbaugh, GE
Taylor, RW
Pfeiffer, DR
机构
[1] Ohio State Univ, Dept Mol Biochem, Columbus, OH 43210 USA
[2] Ohio State Univ, Dept Cellular Biochem, Columbus, OH 43210 USA
[3] Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA
关键词
D O I
10.1289/ehp.8279
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Among divalent cations, the ionophore monensin shows high activity and selectivity for the transport of lead ions (Pb2+) across phospholipid membranes. When coadministered to rats that were receiving meso-dimercaptosucinate for treatment of Pb intoxication, monensin significantly increased the amount of Pb removed from femur, brain, and heart. It showed a tendency to increase Pb removal from liver and kidney but had no effect of this type in skeletal muscle. Tissue levels of several physiologic (calcium, cobalt, copper, iron, magnesium, manganese, molybdenum, zinc) and nonphysiologic (arsenic, cadmium, chromium, nickel, strontium) elements were also determined after the application of these compounds. Among the physiologic elements, a number of significant changes were seen, including both rising and failing values. The size of these changes was typically around 20% compared with control values, with die largest examples seen in femur. These changes often tended to reverse those of similar size that had occurred during Pb administration. Among the nonphysiologic elements, which were present in trace amounts, the changes were smaller in number but larger in size. None of these changes appears likely to be significant in terms of toxicity, and there were no signs of overt toxicity under any of the conditions employed. Monensin may act by cotransporting Pb2+ and OH- ions out of cells, in exchange for external sodium ions. The net effect would be to shuttle intracellular Pb2+ to extracellular dimercaptosuccinic acid thereby enhancing its effectiveness. Thus, monensin may be useful for the treatment of Pb intoxication when applied in combination with hydrophilic Pb2+ chelators.
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页码:484 / 493
页数:10
相关论文
共 51 条
  • [11] Chelated lead in relation to lead in bone and ALAD genotype
    Gerhardsson, L
    Börjesson, J
    Mattsson, S
    Schütz, A
    Skerfving, S
    [J]. ENVIRONMENTAL RESEARCH, 1999, 80 (04) : 389 - 398
  • [12] Chelation therapy in β-thalassemia:: An optimistic update
    Giardina, PJ
    Grady, RW
    [J]. SEMINARS IN HEMATOLOGY, 2001, 38 (04) : 360 - 366
  • [13] LEAD TOXICITY - CURRENT CONCERNS
    GOYER, RA
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 1993, 100 : 177 - 187
  • [14] ROLE OF CHELATING-AGENTS FOR PREVENTION, INTERVENTION, AND TREATMENT OF EXPOSURES TO TOXIC METALS
    GOYER, RA
    CHERIAN, MG
    JONES, MM
    REIGART, JR
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 1995, 103 (11) : 1048 - 1052
  • [15] ROLE OF 2,3-DIMERCAPTOSUCCINIC ACID IN THE TREATMENT OF HEAVY-METAL POISONING
    GRAZIANO, JH
    [J]. MEDICAL TOXICOLOGY AND ADVERSE DRUG EXPERIENCE, 1986, 1 (03): : 155 - 162
  • [16] 2,3-DIMERCAPTOSUCCINIC ACID AS AN ANTIDOTE FOR LEAD-INTOXICATION
    GRAZIANO, JH
    SIRIS, ES
    LOIACONO, N
    SILVERBERG, SJ
    TURGEON, L
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1985, 37 (04) : 431 - 438
  • [17] DOSE-RESPONSE STUDY OF ORAL 2,3-DIMERCAPTOSUCCINIC ACID IN CHILDREN WITH ELEVATED BLOOD LEAD CONCENTRATIONS
    GRAZIANO, JH
    LOLACONO, NJ
    MEYER, P
    [J]. JOURNAL OF PEDIATRICS, 1988, 113 (04) : 751 - 757
  • [18] GRAZIANO JH, 1993, NEUROTOXICOLOGY, V14, P219
  • [19] The ionophore nigericin transports Pb2+ with high activity and selectivity:: A comparison to monensin and ionomycin
    Hamidinia, SA
    Tan, B
    Erdahl, WL
    Chapman, CJ
    Taylor, RW
    Pfeiffer, DR
    [J]. BIOCHEMISTRY, 2004, 43 (50) : 15956 - 15965
  • [20] Monensin mediates a rapid and selective transport of Pb2+ -: Possible application of monensin for the treatment of Pb2+ intoxication
    Hamidinia, SA
    Shimelis, OI
    Tan, B
    Erdahl, WL
    Chapman, CJ
    Renkes, GD
    Taylor, RW
    Pfeiffer, DR
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (41) : 38111 - 38120