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Publication Detail

Title: Thallium Toxicity in Caenorhabditis elegans: Involvement of the SKN-1 Pathway and Protection by S-Allylcysteine.

Authors: Hurtado-Díaz, María Ester; Estrada-Valencia, Rubén; Rangel-López, Edgar; Maya-López, Marisol; Colonnello, Alinne; Galván-Arzate, Sonia; Verstraeten, Sandra V; Karasu, Cimen; Túnez, Isaac; Aschner, Michael; Santamaría, Abel

Published In Neurotox Res, (2020 Aug)

Abstract: Monovalent thallium (Tl+) is a cation that can exert complex neurotoxic patterns in the brain by mechanisms that have yet to be completely characterized. To learn more about Tl+ toxicity, it is necessary to investigate its major effects in vivo and its ability to trigger specific signaling pathways (such as the antioxidant SKN-1 pathway) in different biological models. Caenorhabditis elegans (C. elegans) is a nematode constituting a simple in vivo biological model with a well-characterized nervous system, and high genetic homology to mammalian systems. In this study, both wild-type (N2) and skn-1 knockout (KO) mutant C. elegans strains subjected to acute and chronic exposures to Tl+ [2.5-35 μM] were evaluated for physiological stress (survival, longevity, and worm size), motor alterations (body bends), and biochemical changes (glutathione S-transferase regulation in a gst-4 fluorescence strain). While survival was affected by Tl+ in N2 and skn-1 KO (worms lacking the orthologue of mammalian Nrf2) strains in a similar manner, the longevity was more prominently decreased in the skn-1 KO strain compared with the wild-type strain. Moreover, chronic exposure led to a greater compromise in the longevity in both strains compared with acute exposure. Tl+ also induced motor alterations in both skn-1 KO and wild-type strains, as well as changes in worm size in wild-type worms. In addition, preconditioning nematodes with the well-known antioxidant S-allylcysteine (SAC) reversed the Tl+-induced decrease in survival in the N2 strain. GST fluorescent expression was also decreased by the metal in the nematode, and recovered by SAC. Our results describe and validate, for the first time, features of the toxic pattern induced by Tl+ in an in vivo biological model established with C. elegans, supporting an altered redox component in Tl+ toxicity, as previously described in mammal models. We demonstrate that the presence of the orthologous SKN-1 pathway is required for worms in evoking an efficient antioxidant defense. Therefore, the nematode represents an optimal model to reproduce mammalian Tl+ toxicity, where toxic mechanisms and novel therapeutic approaches of clinical value may be successfully pursued.

PubMed ID: 32468422 Exiting the NIEHS site

MeSH Terms: Animals; Animals, Genetically Modified; Antioxidants/pharmacology*; Body Size/drug effects*; Caenorhabditis elegans Proteins/drug effects*; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Caenorhabditis elegans/drug effects; Caenorhabditis elegans/growth & development; Cysteine/analogs & derivatives*; Cysteine/pharmacology; DNA-Binding Proteins/drug effects*; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Gene Knockout Techniques; Glutathione Transferase/drug effects; Glutathione Transferase/metabolism; Longevity/drug effects*; Organometallic Compounds/toxicity*; Transcription Factors/drug effects*; Transcription Factors/genetics; Transcription Factors/metabolism

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