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01-06-2020 | Helminths | Original Article

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

Authors: Tao Ke, Julia Bornhorst, Tanja Schwerdtle, Abel Santamaría, Félix Alexandre Antunes Soare, João B. T. Rocha, Marcelo Farina, Aaron B. Bowman, Michael Aschner

Published in: Neurotoxicity Research | Issue 1/2020

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.

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Title: Therapeutic Efficacy of the N,N′ Bis-(2-Mercaptoethyl) Isophthalamide Chelator for Methylmercury Intoxication in Caenorhabditis elegans
Authors: Tao Ke
Julia Bornhorst
Tanja Schwerdtle
Abel Santamaría
Félix Alexandre Antunes Soare
João B. T. Rocha
Marcelo Farina
Aaron B. Bowman
Michael Aschner
Publication date: 01-06-2020
Publisher: Springer US
Keywords: Helminths
Intoxication
Published in: Neurotoxicity Research / Issue 1/2020
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-020-00194-0

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

Abstract

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Abstract

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