Comparison of the Toxic Effects of Quinolinic Acid and 3-Nitropropionic Acid in C. elegans: Involvement of the SKN-1 Pathway

Ilan Kotlar, Aline Colonnello, María Fernanda Aguilera-González, Daiana Silva Avila, María Eduarda de Lima, Rodolfo García-Contreras, Alma Ortíz-Plata, Félix Alexandre Antunes Soares, Michael Aschner, Abel Santamaría

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The tryptophan metabolite, quinolinic acid (QUIN), and the mitochondrial toxin 3-nitropropionic acid (3-NP) are two important tools for toxicological research commonly used in neurotoxic models of excitotoxicity, oxidative stress, energy depletion, and neuronal cell death in mammals. However, their toxic properties have yet to be explored in the nematode Caenorhabditis elegans (C. elegans) for the establishment of novel, simpler, complementary, alternative, and predictive neurotoxic model of mammalian neurotoxicity. In this work, the effects of QUIN (1–100 mM) and 3-NP (1–10 mM) were evaluated on various physiological parameters (survival, locomotion, and longevity) in a wild-type (WT) strand of C. elegans (N2). Their effects were also tested in the VC1772 strain (knock out for the antioxidant SKN-1 pathway) and the VP596 strain (worms with a reporter gene for glutathione S-transferase (GST) transcription) in order to establish the role of the SKN-1 pathway in the mode of action of QUIN and 3-NP. In N2, the higher doses of both toxins decreased survival, though only QUIN altered motor activity. Both toxins also reduced longevity in the VC1772 strain (as compared to N2 strain) and augmented GST transcription in the VP596 strain at the highest doses. The changes induced by both toxins require high doses, and therefore appear moderate when compared with other toxic agents. Nevertheless, the alterations produced by QUIN and 3-NP in C. elegans are relevant to mammalian neurotoxicity as they provide novel mechanistic approaches to the assessment of neurotoxic events comprising oxidative stress and excitotoxicity, in the nematode model.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalNeurotoxicity Research
DOIs
Publication statusAccepted/In press - Aug 18 2017

    Fingerprint

Keywords

  • Excitotoxicity
  • Huntington’s disease
  • NMDA
  • SKN-1
  • VC1772
  • VP596

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Kotlar, I., Colonnello, A., Aguilera-González, M. F., Avila, D. S., de Lima, M. E., García-Contreras, R., ... Santamaría, A. (Accepted/In press). Comparison of the Toxic Effects of Quinolinic Acid and 3-Nitropropionic Acid in C. elegans: Involvement of the SKN-1 Pathway. Neurotoxicity Research, 1-9. https://doi.org/10.1007/s12640-017-9794-x