Please use this identifier to cite or link to this item:
Title: Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans.
Authors: Salgueiro, Willian G
Goldani, Bruna S
Peres, Tanara V
Miranda-Vizuete, Antonio
Aschner, Michael
da Rocha, João Batista Teixeira
Alves, Diego
Ávila, Daiana S
Keywords: Cytoprotection;DAF-16/FOXO;Organoselenium;Organotellurium;Quinoline;SKN-1/Nrf2;Thioredoxin reductase 1
metadata.dc.subject.mesh: Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins
DNA-Binding Proteins
Forkhead Transcription Factors
Gene Expression Regulation
NF-E2-Related Factor 2
Organometallic Compounds
Organoselenium Compounds
Oxidative Stress
Signal Transduction
Superoxide Dismutase
Transcription Factors
Issue Date: 30-May-2017
Abstract: Organic selenium and tellurium compounds are known for their broad-spectrum effects in a variety of experimental disease models. However, these compounds commonly display high toxicity and the molecular mechanisms underlying these deleterious effects have yet to be elucidated. Thus, the need for an animal model that is inexpensive, amenable to high-throughput analyses, and feasible for molecular studies is highly desirable to improve organochalcogen pharmacological and toxicological characterization. Herein, we use Caenorhabdtis elegans (C. elegans) as a model for the assessment of pharmacological and toxicological parameters following exposure to two 4-phenylchalcogenil-7-chloroquinolines derivatives (PSQ for selenium and PTQ for tellurium-containing compounds). While non-lethal concentrations (NLC) of PTQ and PSQ attenuated paraquat-induced effects on survival, lifespan and oxidative stress parameters, lethal concentrations (LC) of PTQ and PSQ alone are able to impair these parameters in C. elegans. We also demonstrate that DAF-16/FOXO and SKN-1/Nrf2 transcription factors underlie the mechanism of action of these compounds, as their targets sod-3, gst-4 and gcs-1 were modulated following exposures in a daf-16- and skn-1-dependent manner. Finally, in accordance with a disturbed thiol metabolism in both LC and NLC, we found higher sensitivity of trxr-1 worm mutants (lacking the selenoprotein thioredoxin reductase 1) when exposed to PSQ. Finally, our study suggests new targets for the investigation of organochalcogen pharmacological effects, reinforcing the use of C. elegans as a powerful platform for preclinical approaches.
metadata.dc.identifier.doi: 10.1016/j.freeradbiomed.2017.05.020
Appears in Collections:Producción 2020

Files in This Item:
There are no files associated with this item.

This item is protected by original copyright

Except where otherwise noted, Items on the Andalusian Health Repository site are licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives License.