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Shawn A. Hamidinia,¹ Warren L. Erdahl,¹ Clifford J. Chapman,¹ Gregory E. Steinbaugh,¹ Richard W. Taylor,² and Douglas R. Pfeiffer¹

¹Departments of Molecular and Cellular Biochemistry, Ohio State University, Columbus, Ohio, USA; ²Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA

Abstract
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. Key words: chelation therapy, DMSA, heavy metal intoxication, ICP mass spectroscopy, ionophores, monensin, Pb, Pb²⁺ transport, trace metal cations. Environ Health Perspect 114:484-493 (2006) . doi:10.1289/ehp.8279 available via http://dx.doi.org/ [Online 29 September 2005]

Address correspondence to D.R. Pfeiffer, Department of Molecular and Cellular Biochemistry, Ohio State University, 1645 Neil Ave., 310A Hamilton Hall, Columbus, Ohio 43210-1218. Telephone: (614) 292-8774. Fax: (614) 292-4118. E-mail: pfeiffer.17@osu.edu

This research was supported by grant GM 66206 from the National Institutes of General Medical Sciences, National Institutes of Health ; by grant 0255017B from the American Heart Association, Ohio Valley Affiliate ; and by grant HR00-030 from the Oklahoma Center for the Advancement of Science and Technology.

The authors declare they have no competing financial interests.

Received 3 May 2005 ; accepted 29 September 2005.