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Therapeutic Efficacy of the N,N′ Bis-(2-Mercaptoethyl) Isophthalamide Chelator for Methylmercury Intoxication in Caenorhabditis elegans.

Therapeutic Efficacy of the N,N′ Bis-(2-Mercaptoethyl) Isophthalamide Chelator for Methylmercury Intoxication in Caenorhabditis elegans.

Authors :
Ke, Tao
Bornhorst, Julia
Schwerdtle, Tanja
Santamaría, Abel
Soare, Félix Alexandre Antunes
Rocha, João B. T.
Farina, Marcelo
Bowman, Aaron B.
Aschner, Michael
Source :
Neurotoxicity Research. Jun2020, Vol. 38 Issue 1, p133-144. 12p.
Publication Year :
2020

Abstract

Methylmercury (MeHg) is a global pollutant and potent neurotoxin. In humans, MeHg damages the central nervous system (CNS), causing irreversible neuronal shrinkage, and neuronal loss. Most chelators for clinical mercury detoxification are thiol-containing agents. N,N 'bis-(2-mercaptoethyl) isophthalamide (NBMI) is a lipophilic thiol agent synthesized from natural chemicals. NBMI has high affinity for mercury, cadmium and lead, and can decrease their concentrations in polluted water. However, the efficacy of NBMI for MeHg toxicity has yet to be evaluated in intact animals. Here we used the nematode Caenorhabditis elegans (C. elegans) to test the efficacy of NBMI in attenuating MeHg toxicity in vivo in the whole organism. The results showed that NBMI reduced both the acute toxicity (125 μM MeHg, 1 h) and chronic (5 μM MeHg, 24 h) MeHg toxicity. Co-treatment with NBMI achieved maximal efficacy against MeHg toxicity, however delayed treatment 6 days after initiation of exposure was also effective at reducing neurotoxicity. Co-treatment of NBMI reduced the worms' death rate, structural damage in DAergic neurons, and restored antioxidant response levels. While this study provides proof of principle for the therapeutic value of NBMI in MeHg toxicity, future studies are needed to address the cellular and molecular mechanisms and translatability of these effects to humans and other animals. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10298428
Volume :
38
Issue :
1
Database :
Academic Search Index
Journal :
Neurotoxicity Research
Publication Type :
Academic Journal
Accession number :
143359398
Full Text :
https://doi.org/10.1007/s12640-020-00194-0