TY  - JOUR
AU  - Nurchi, Valeria M.
AU  - Buha-Đorđević, Aleksandra
AU  - Crisponi, Guido
AU  - Alexander, Jan
AU  - Bjørklund, Geir
AU  - Aaseth, Jan
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3518
AB  - High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As2+ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As2+-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.
PB  - MDPI AG
T2  - Biomolecules
T1  - Arsenic toxicity: Molecular targets and therapeutic agents
VL  - 10
IS  - 2
DO  - 10.3390/biom10020235
ER  - 

@article{
author = "Nurchi, Valeria M. and Buha-Đorđević, Aleksandra and Crisponi, Guido and Alexander, Jan and Bjørklund, Geir and Aaseth, Jan",
year = "2020",
abstract = "High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As2+ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As2+-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.",
publisher = "MDPI AG",
journal = "Biomolecules",
title = "Arsenic toxicity: Molecular targets and therapeutic agents",
volume = "10",
number = "2",
doi = "10.3390/biom10020235"
}

Nurchi, V. M., Buha-Đorđević, A., Crisponi, G., Alexander, J., Bjørklund, G.,& Aaseth, J.. (2020). Arsenic toxicity: Molecular targets and therapeutic agents. in Biomolecules
MDPI AG., 10(2).
https://doi.org/10.3390/biom10020235

Nurchi VM, Buha-Đorđević A, Crisponi G, Alexander J, Bjørklund G, Aaseth J. Arsenic toxicity: Molecular targets and therapeutic agents. in Biomolecules. 2020;10(2).
doi:10.3390/biom10020235 .

Nurchi, Valeria M., Buha-Đorđević, Aleksandra, Crisponi, Guido, Alexander, Jan, Bjørklund, Geir, Aaseth, Jan, "Arsenic toxicity: Molecular targets and therapeutic agents" in Biomolecules, 10, no. 2 (2020),
https://doi.org/10.3390/biom10020235 . .

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 . .