Salgueiro, Willian GGoldani, Bruna SPeres, Tanara VMiranda-Vizuete, AntonioAschner, Michaelda Rocha, João Batista TeixeiraAlves, DiegoÁvila, Daiana S2023-01-252023-01-252017-05-30http://hdl.handle.net/10668/11257Organic 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.enCytoprotectionDAF-16/FOXOOrganoseleniumOrganotelluriumQuinolineSKN-1/Nrf2Thioredoxin reductase 1AnimalsAntioxidantsCaenorhabditis elegansCaenorhabditis elegans ProteinsChalcogensDNA-Binding ProteinsForkhead Transcription FactorsGene Expression RegulationLongevityNF-E2-Related Factor 2Organometallic CompoundsOrganoselenium CompoundsOxidantsOxidative StressParaquatQuinolinesSignal TransductionSuperoxide DismutaseTelluriumTranscription FactorsInsights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans.research article28571752open access10.1016/j.freeradbiomed.2017.05.0201873-4596https://doi.org/10.1016/j.freeradbiomed.2017.05.020