Monensin improves the effectiveness of meso-dimercaptosuccinate when used to treat lead intoxication in rats.
Monensin improves the effectiveness of meso-dimercaptosuccinate when used to treat lead intoxication in rats.
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当用来治疗大鼠铅中毒时，Monensin提高了中二秒核酸酯的有效性。
DOI：
10.1289/ehp.8279
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发表时间：
2006-04
影响因子：
10.4
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中科院分区：
文献类型：
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在二价阳离子中，离子载体莫能菌素对铅离子（Pb 2+）跨磷脂膜的运输显示出高活性和选择性。当共同管理的大鼠接受meso-二巯基琥珀酸治疗铅中毒，莫能菌素显着增加的量从股骨，大脑和心脏的铅。它显示出增加铅从肝脏和肾脏中的去除的趋势，但在骨骼肌中没有这种类型的效果。组织水平的几个生理（钙，钴，铜，铁，镁，锰，钼，锌）和非生理（砷，镉，铬，镍，锶）元素后，这些化合物的应用程序也进行了测定。在生理元素中，观察到一些显著变化，包括上升和下降的值。与对照值相比，这些变化的大小通常约为20%，在股骨中观察到最大的例子。这些变化往往倾向于扭转那些类似的大小，发生在铅管理。在微量存在的非生理元素中，变化数量较少，但规模较大。在毒性方面，这些变化似乎都不太可能是显著的，并且在所采用的任何条件下都没有明显毒性的迹象。莫能菌素可能通过将Pb 2+和OH-离子共转运出细胞，以交换外部钠离子而起作用。净效应将是将细胞内Pb 2+穿梭到细胞外二巯基琥珀酸，从而增强其有效性。因此，当与亲水性Pb 2+螯合剂组合应用时，莫能菌素可用于治疗Pb中毒。
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-dimercaptosuccinate 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 falling values. The size of these changes was typically around 20% compared with control values, with the 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.