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Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans.
Free Radic Biol Med. 2017 09; 110:133-141.FR

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.

Authors+Show Affiliations

Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCE),Universidade Federal do Pampa - UNIPAMPA, CEP 97500-970 Uruguaiana, RS, Brazil.Laboratório de Síntese Orgânica Limpa - LASOL - CCQFA - Universidade Federal de Pelotas - UFPel, CEP 96010-900 Pelotas, RS, Brazil.Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain.Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.Departamento de Bioquímica e Biologia Molecular, CCNE, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.Laboratório de Síntese Orgânica Limpa - LASOL - CCQFA - Universidade Federal de Pelotas - UFPel, CEP 96010-900 Pelotas, RS, Brazil.Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCE),Universidade Federal do Pampa - UNIPAMPA, CEP 97500-970 Uruguaiana, RS, Brazil. Electronic address: avilads1@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28571752

Citation

Salgueiro, Willian G., et al. "Insights Into the Differential Toxicological and Antioxidant Effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis Elegans." Free Radical Biology & Medicine, vol. 110, 2017, pp. 133-141.
Salgueiro WG, Goldani BS, Peres TV, et al. Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans. Free Radic Biol Med. 2017;110:133-141.
Salgueiro, W. G., Goldani, B. S., Peres, T. V., Miranda-Vizuete, A., Aschner, M., da Rocha, J. B. T., Alves, D., & Ávila, D. S. (2017). Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans. Free Radical Biology & Medicine, 110, 133-141. https://doi.org/10.1016/j.freeradbiomed.2017.05.020
Salgueiro WG, et al. Insights Into the Differential Toxicological and Antioxidant Effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis Elegans. Free Radic Biol Med. 2017;110:133-141. PubMed PMID: 28571752.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans. AU - Salgueiro,Willian G, AU - Goldani,Bruna S, AU - Peres,Tanara V, AU - Miranda-Vizuete,Antonio, AU - Aschner,Michael, AU - da Rocha,João Batista Teixeira, AU - Alves,Diego, AU - Ávila,Daiana S, Y1 - 2017/05/30/ PY - 2016/12/18/received PY - 2017/05/18/revised PY - 2017/05/24/accepted PY - 2017/6/3/pubmed PY - 2018/4/13/medline PY - 2017/6/3/entrez KW - Cytoprotection KW - DAF-16/FOXO KW - Organoselenium KW - Organotellurium KW - Quinoline KW - SKN-1/Nrf2 KW - Thioredoxin reductase 1 SP - 133 EP - 141 JF - Free radical biology & medicine JO - Free Radic. Biol. Med. VL - 110 N2 - 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. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/28571752/Insights_into_the_differential_toxicological_and_antioxidant_effects_of_4_phenylchalcogenil_7_chloroquinolines_in_Caenorhabditis_elegans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(17)30593-2 DB - PRIME DP - Unbound Medicine ER -