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Heavy Metal Ion Transport Utilizing Natural and Synthetic Ionophores false
By:Gregory E. Steinbaugh
Published on 2007 by

Abstract: Heavy metal poisoning is still a prevalent problem in society. Current chelation therapies are only partially effective at removing Pb from soft tissues and are ineffective at removing Pb from bone. Our laboratory discovered that the sodium ionophore monensin is selective at transporting Pb2 into model phospholipid bilayer vesicles, while it does not transport other divalent cations. Monensin mediated Pb transport was initially a concern because this particular ionophore is used in agriculture as an anticoccidial agent and to promote weight gain in cattle. It appeared then that monensin contaminated animals might serve as an entryway for Pb into humans. Regarding previously accumulated Pb, our work using rats did not support this possibility. Administration of monensin, in combination with the chelating agent DMSA, produced reduced levels in liver, kidney, brain, femur, heart, and skeletal muscle. This occurred while the levels of endogenous metals such as Ca2, Mg2, and Zn2+ were relatively unchanged. We also tested the Pb transport and removal of some other ionophores, including salinomycin, lasalocid, and nigericin, and observed that monensin, salinomycin, and lasalocid also lowered Pb concentrations in all organs examined, whereas nigericin caused a significant increase. This is thought to be due to Na+ and K+ gradients that exist across the plasma membrane of cells. A Kemp's triacid derivative of a 15-crown-5 ether was found to transport both Pb2+ and Cd2+ in an artificial membrane system. There is a stoichiometry of 1:1 between either Pb2+ or Cd2+ and the crown ether derivative while at lower metal concentrations, it was observed that comproportionation occurs until a certain metal concentration is reached. Based on our work, KTC 15-cr-5 ether could be used for the treatment of heavy metal intoxication and in the treatment of waste water. During the course of our studies, we also observed that rats which were administered Pb by IP injection had a smaller statistical difference when compared to animals that were administered Pb orally.

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