論文 - 詳細
| RRC ID | 51400 |
|---|---|
| 著者 | Salgueiro WG, Goldani BS, Peres TV, Miranda-Vizuete A, Aschner M, da Rocha JBT, Alves D, Ávila DS. |
| タイトル | Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans. |
| ジャーナル | Free Radic Biol Med |
| 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. |
| 巻・号 | 110 |
| ページ | 133-141 |
| 公開日 | 2017-9-1 |
| DOI | 10.1016/j.freeradbiomed.2017.05.020 |
| PII | S0891-5849(17)30593-2 |
| PMID | 28571752 |
| MeSH | Animals Antioxidants / chemical synthesis Antioxidants / pharmacology* Caenorhabditis elegans / drug effects* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Chalcogens / chemical synthesis Chalcogens / pharmacology* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism Gene Expression Regulation Longevity / drug effects NF-E2-Related Factor 2 / genetics NF-E2-Related Factor 2 / metabolism Organometallic Compounds / chemical synthesis Organometallic Compounds / pharmacology* Organoselenium Compounds / chemical synthesis Organoselenium Compounds / pharmacology* Oxidants / antagonists & inhibitors Oxidants / toxicity Oxidative Stress Paraquat / antagonists & inhibitors Paraquat / toxicity Quinolines / chemical synthesis Quinolines / pharmacology* Signal Transduction Superoxide Dismutase / genetics Superoxide Dismutase / metabolism Tellurium / pharmacology* Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 6.17 |
| 引用数 | 23 |
| リソース情報 | |
| 線虫 | tm760 |