Testing of chelating agents and vitamins against lead toxicity using mammalian cell cultures†

Abstract

Mammalian cell cultures were used to determine the capacity of antidotes to modify (a) lead uptake, (b) lead toxicity and (c) lead release from cells. The following chelating agents were tested: Na, Ca-ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), nitriloacetic acid, ethylene glycol-bis(aminoethyl)tetraacetic acid (EGTA), D,L-mercaptosuccinic acid (MSA), meso-2,3-dimercaptopropanesuccinic acid (MSA), D,L-2,3-dimercaptopropane-1-sulfonic acid (DMPS), penicillamine (PA), N-acetylpenicillamine (NAPA), and diethylcarbodithioate (DDTC). The following vitamins were tested: thiamine (B1), riboflavine (B2), pyridoxine (B6), cobalamin (B12) and ascorbic acid (C). Inhibition of lead uptake was produced by EDTA, EGTA, DMSA, DMPS, MSA, PA, NAPA and vitamins B1, B6 and C, vitamins B2 and B12 being ineffective. The same compounds reduced lead cytotoxicity. Interestingly DDTC and DTPA increased lead uptake, but did not exacerbate lead toxicity. Significant release of lead from preloaded cells was caused by DTPA, NAPA, DMPS and PA, while the other chelators were ineffective.

Strategies for Safe and Effective Therapeutic Measures for Chronic Arsenic and Lead Poisoning

“…This passage can be accomplished either (a) by passing through the lipid part of the membrane as an uncharged molecule or (b) by utilizing one of the anion/ cation transport systems present in the membrane 4) . There is a hypothesis that a large ion complex with a positive charge will pass out of a cell very slowly because of its inability to pass through either the lipid portion of the cellular membrane or the cation transport system designed to move ions with a +1 or a +2 charge across the membrane 3,4) . Another important property of metal complexes is the stereochemistry of the toxic metal ion.…”

“…Despite these encouraging reports, there are still no clinical reports a v a i l a b l e o n t h e e ff e c t o f d i e t a r y t h i a m i n e supplementation on lead toxicity. Thiamine as a complementary therapeutic agent or an 'adjuvant' to a conventional metal chelating agent has been tried 145,146) . Thiamine administration concomitantly with CaNa 2 EDTA enhanced the efficacy of a chelator to potentiate urinary lead excretion, to reduce tissue lead including brain lead and restore lead induced biochemical alterations [147][148][149][150] .…”

“…The breakthrough in the development of chelation therapy came after the introduction of ethylene diamine tetraacetic acid (EDTA), initially to combat lead intoxication. The value of EDTA as a clinical chelating agent was reduced by the need for slow intravenous administration, low intestinal uptake, exclusive extracellular action and high stability constants with essential metals 3) .…”

Interaction of Pb2+, PbMe22+ and PbPh22+ with 3-(phenyl)-2-sulfanylpropenoic acid: A coordinative and toxicological approach

“…The insignificant effect of vitamin B 6 alone is in contrast with the protective effect shown by this vitamin when Chinese hamster peritoneal cells were cultured in a medium containing a mixture of the vitamin and Pb 2+ [54].…”

Crystal Structure of 1,3,5-Tri(4-chlorophenyl)carbamoylurea

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As promising chelating agents for the treatment of lead and mercury poisoning in humans, [1][2][3][4] we are currently working on the synthesis of 4,5-dicarbonyl exo-heterocyclic compounds, such as 1,3-di(p-chlorophenyl)imidazolidinetrione. During the preparation of this compound, an intermediate was obtained as shiny crystals; spectroscopic data (NMR, UV and IR) suggest its structure.

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