TY - JOUR
T1 - Comparison of the Toxic Effects of Quinolinic Acid and 3-Nitropropionic Acid in C. elegans
T2 - Involvement of the SKN-1 Pathway
AU - Kotlar, Ilan
AU - Colonnello, Aline
AU - Aguilera-González, María Fernanda
AU - Avila, Daiana Silva
AU - de Lima, María Eduarda
AU - García-Contreras, Rodolfo
AU - Ortíz-Plata, Alma
AU - Soares, Félix Alexandre Antunes
AU - Aschner, Michael
AU - Santamaría, Abel
N1 - Publisher Copyright:
© 2017, Springer Science+Business Media, LLC.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - Excitotoxicity
KW - Huntington’s disease
KW - NMDA
KW - SKN-1
KW - VC1772
KW - VP596
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U2 - 10.1007/s12640-017-9794-x
DO - 10.1007/s12640-017-9794-x
M3 - Article
C2 - 28822104
AN - SCOPUS:85027731811
SN - 1029-8428
VL - 33
SP - 259
EP - 267
JO - Neurotoxicity Research
JF - Neurotoxicity Research
IS - 2
ER -