RT Journal Article
T1 Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans.
A1 Salgueiro, Willian G
A1 Goldani, Bruna S
A1 Peres, Tanara V
A1 Miranda-Vizuete, Antonio
A1 Aschner, Michael
A1 da Rocha, João Batista Teixeira
A1 Alves, Diego
A1 Ávila, Daiana S
K1 Cytoprotection
K1 DAF-16/FOXO
K1 Organoselenium
K1 Organotellurium
K1 Quinoline
K1 SKN-1/Nrf2
K1 Thioredoxin reductase 1
AB 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.
YR 2017
FD 2017-05-30
LK http://hdl.handle.net/10668/11257
UL http://hdl.handle.net/10668/11257
LA en
DS RISalud
RD Apr 12, 2025