Effects of chelators on mercury, iron, and lead neurotoxicity in cortical culture.
Chelation therapy for the treatment of acute, high dose exposure to heavy metals is accepted medical practice. However, a much wider use of metal chelators is by alternative health practitioners for so called "chelation therapy". Given this widespread and largely unregulated use of metal chelators it is important to understand the actions of these compounds. We tested the effects of four commonly used metal chelators, calcium disodium ethylenediaminetetraacetate (CaNa2EDTA), D-penicillamine (DPA), 2,3 dimercaptopropane-1-sulfonate (DMPS), and dimercaptosuccinic acid (DMSA) for their effects on heavy metal neurotoxicity in primary cortical cultures. We studied the toxicity of three forms of mercury, inorganic mercury (HgCl2), methyl mercury (MeHg), and ethyl mercury (thimerosal), as well as lead (PbCl2) and iron (Fe-citrate). DPA had the worst profile of effects, providing no protection while potentiating HgCl2, thimerosal, and Fe-citrate toxicity. DMPS and DMSA both attenuated HgCl2 toxicity and potentiated thimerosal and Fe toxicity, while DMPS also potentiated PbCl2 toxicity. CaNa2EDTA attenuated HgCl2 toxicity, but caused a severe potentiation of Fe-citrate toxicity. The ability of these chelators to attenuate the toxicity of various metals is quite restricted, and potentiation of toxicity is a serious concern. Specifically, protection is provided only against inorganic mercury, while it is lacking against the common form of mercury found in food, MeHg, and the form found in vaccines, thimerosal. The potentiation of Fe-citrate toxicity is of concern because of iron's role in oxidative stress in the body. Potentiation of iron toxicity could have serious health consequences when using chelation therapy.
Rush
Travis
T
Department of Biomedical Sciences, Marquette University, 561 N. 15th Street, Rm 464, Milwaukee, WI 53233, USA.
Hjelmhaug
Julie
J
Lobner
Doug
D
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004492:Edetic Acid / Q000494:pharmacology*; D005260:Female; D007501:Iron / Q000037:antagonists & inhibitors*; D007854:Lead / Q000037:antagonists & inhibitors*; D008627:Mercuric Chloride / Q000037:antagonists & inhibitors*; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors; D051379:Mice; D010396:Penicillamine / Q000494:pharmacology*; D011247:Pregnancy; D004113:Succimer / Q000494:pharmacology*; D013849:Thimerosal / Q000037:antagonists & inhibitors; D014494:Unithiol / Q000494:pharmacology
D002614:Chelating Agents; D008767:Methylmercury Compounds; D013849:Thimerosal; D007854:Lead; D014494:Unithiol; C029891:lead chloride; D008627:Mercuric Chloride; D004492:Edetic Acid; D004113:Succimer; D007501:Iron; D010396:Penicillamine; C004925:methylmercuric chloride