Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans

Willian G. Salgueiro, Bruna S. Goldani, Tanara V. Peres, Antonio Miranda-Vizuete, Michael Aschner, João Batista Teixeira da Rocha, Diego Alves, Daiana S. Ávila

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)133-141
Number of pages9
JournalFree Radical Biology and Medicine
Volume110
DOIs
StatePublished - Sep 1 2017

Fingerprint

Caenorhabditis elegans
Tellurium
Toxicology
Antioxidants
Pharmacology
Tellurium compounds
Thioredoxin Reductase 1
Selenium compounds
Selenium Compounds
Selenoproteins
Paraquat
Oxidative stress
Selenium
Sulfhydryl Compounds
Metabolism
Toxicity
Animals
Oxidative Stress
Transcription Factors
Theoretical Models

Keywords

  • Cytoprotection
  • DAF-16/FOXO
  • Organoselenium
  • Organotellurium
  • Quinoline
  • SKN-1/Nrf2
  • Thioredoxin reductase 1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans. / Salgueiro, Willian G.; Goldani, Bruna S.; Peres, Tanara V.; Miranda-Vizuete, Antonio; Aschner, Michael; da Rocha, João Batista Teixeira; Alves, Diego; Ávila, Daiana S.

In: Free Radical Biology and Medicine, Vol. 110, 01.09.2017, p. 133-141.

Research output: Contribution to journalArticle

Salgueiro, Willian G. ; Goldani, Bruna S. ; Peres, Tanara V. ; Miranda-Vizuete, Antonio ; Aschner, Michael ; da Rocha, João Batista Teixeira ; Alves, Diego ; Ávila, Daiana S. / Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans. In: Free Radical Biology and Medicine. 2017 ; Vol. 110. pp. 133-141.
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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.",
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AU - Peres, Tanara V.

AU - Miranda-Vizuete, Antonio

AU - Aschner, Michael

AU - da Rocha, João Batista Teixeira

AU - Alves, Diego

AU - Ávila, Daiana S.

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