Monensin improves the effectiveness of meso-dimercaptosuccinate when used to treat lead intoxication in rats.
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.
Hamidinia
Shawn A
SA
Departments of Molecular and Cellular Biochemistry, Ohio State University, Columbus, Ohio, USA.
Erdahl
Warren L
WL
Chapman
Clifford J
CJ
Steinbaugh
Gregory E
GE
Taylor
Richard W
RW
Pfeiffer
Douglas R
DR
D000818:Animals; D004357:Drug Synergism; D007855:Lead Poisoning / Q000188:drug therapy*; D008297:Male; D008985:Monensin / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D004113:Succimer / Q000627:therapeutic use*
D008985:Monensin; D004113:Succimer