The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg. Its toxicity is also lower than that of DMPS (dimercaptopropane sulfonate), although DMPS is the recommended agent in acute poisonings with Hg salts. It is suggested that intracellular Cd deposits and cerebral deposits of inorganic Hg, to some extent, can be mobilized by a combination of antidotes, but clinical experience with such combinations are lacking. Alpha-lipoic acid (α-LA) has been suggested for toxic metal detoxification but is not considered a drug of choice in clinical pr...actice. The molecular mechanisms and chemical equilibria of complex formation of the chelators with the metal ions Hg2+, Cd2+, and Pb2+ are reviewed since insight into these reactions can provide a basis for further development of therapeutics.
Keywords:
BAL / DMPS / DMSA / Metal chelator / Metal ion
Source:
Molecules, 2019, 24, 3247, 1-32
Publisher:
MDPI
Funding / projects:
VMN thanks Regione Autonoma della Sardegna - RASSR79857 “Metallo-farmaci innovativi: biotrasformazione e target biologici. Un approccio integrato”.
Innovation Sciences and Technologies
(PON RI 2014-2020) at the University of Cagliari.
TY - JOUR
AU - Bjørklund, Geir
AU - Crisponi, Guido
AU - Nurchi, Valeria Marina
AU - Cappai, Rosita
AU - Buha-Đorđević, Aleksandra
AU - Aaseth, Jan
PY - 2019
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3460
AB - The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg. Its toxicity is also lower than that of DMPS (dimercaptopropane sulfonate), although DMPS is the recommended agent in acute poisonings with Hg salts. It is suggested that intracellular Cd deposits and cerebral deposits of inorganic Hg, to some extent, can be mobilized by a combination of antidotes, but clinical experience with such combinations are lacking. Alpha-lipoic acid (α-LA) has been suggested for toxic metal detoxification but is not considered a drug of choice in clinical practice. The molecular mechanisms and chemical equilibria of complex formation of the chelators with the metal ions Hg2+, Cd2+, and Pb2+ are reviewed since insight into these reactions can provide a basis for further development of therapeutics.
PB - MDPI
T2 - Molecules
T1 - A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead
VL - 24
IS - 3247
SP - 1
EP - 32
DO - 10.3390/molecules24183247
ER -
@article{
author = "Bjørklund, Geir and Crisponi, Guido and Nurchi, Valeria Marina and Cappai, Rosita and Buha-Đorđević, Aleksandra and Aaseth, Jan",
year = "2019",
abstract = "The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg. Its toxicity is also lower than that of DMPS (dimercaptopropane sulfonate), although DMPS is the recommended agent in acute poisonings with Hg salts. It is suggested that intracellular Cd deposits and cerebral deposits of inorganic Hg, to some extent, can be mobilized by a combination of antidotes, but clinical experience with such combinations are lacking. Alpha-lipoic acid (α-LA) has been suggested for toxic metal detoxification but is not considered a drug of choice in clinical practice. The molecular mechanisms and chemical equilibria of complex formation of the chelators with the metal ions Hg2+, Cd2+, and Pb2+ are reviewed since insight into these reactions can provide a basis for further development of therapeutics.",
publisher = "MDPI",
journal = "Molecules",
title = "A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead",
volume = "24",
number = "3247",
pages = "1-32",
doi = "10.3390/molecules24183247"
}
Bjørklund, G., Crisponi, G., Nurchi, V. M., Cappai, R., Buha-Đorđević, A.,& Aaseth, J.. (2019). A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead. in Molecules
MDPI., 24(3247), 1-32.
https://doi.org/10.3390/molecules24183247
Bjørklund G, Crisponi G, Nurchi VM, Cappai R, Buha-Đorđević A, Aaseth J. A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead. in Molecules. 2019;24(3247):1-32.
doi:10.3390/molecules24183247 .
Bjørklund, Geir, Crisponi, Guido, Nurchi, Valeria Marina, Cappai, Rosita, Buha-Đorđević, Aleksandra, Aaseth, Jan, "A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead" in Molecules, 24, no. 3247 (2019):1-32,
https://doi.org/10.3390/molecules24183247 . .
