Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in Caenorhabditis elegans by preventing oxidative stress

Daiana Silva Avila, Alexandre Benedetto, Catherine Au, Flávia Manarin, Keith Erikson, Felix Antunes Soares, João Batista Teixeira Rocha, Michael Aschner

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Organochalcogens have been widely studied given their antioxidant activity, which confers neuroprotection, antiulcer, and antidiabetic properties. Given the complexity of mammalian models, understanding the cellular and molecular effects of organochalcogens has been hampered. The nematode worm Caenorhabditis elegans is an alternative experimental model that affords easy genetic manipulations, green fluorescent protein tagging, and in vivo live analysis of toxicity. We previously showed that manganese (Mn)-exposed worms exhibit oxidative-stress-induced neurodegeneration and life-span reduction. Here we use Mn-exposed worms as a model for an oxidatively challenged organism to investigate the underlying mechanisms of organochalcogen antioxidant properties. First, we recapitulate in C. elegans the effects of organochalcogens formerly observed in mice, including their antioxidant activity. This is followed by studies on the ability of these compounds to afford protection against Mn-induced toxicity. Diethyl-2-phenyl-2-tellurophenyl vinyl phosphonate (DPTVP) was the most efficacious compound, fully reversing the Mn-induced reduction in survival and life span. Ebselen was also effective, reversing the Mn-induced reduction in survival and life span, but to a lesser extent compared with DPTVP. DPTVP also lowered Mn-induced increases in oxidant levels, indicating that the increased survival associated with exposure to this compound is secondary to a decrease in oxidative stress. Furthermore, DPTVP induced nuclear translocation of the transcriptional factor DAF-16/FOXO, which regulates stress responsiveness and aging in worms. Our findings establish that the organochalcogens DPTVP and ebselen act as antiaging agents in a model of Mn-induced toxicity and aging by regulating DAF-16/FOXO signaling and attenuating oxidative stress.

Original languageEnglish (US)
Pages (from-to)1903-1910
Number of pages8
JournalFree Radical Biology and Medicine
Volume52
Issue number9
DOIs
StatePublished - May 1 2012
Externally publishedYes

Fingerprint

Organoselenium Compounds
Oxidative stress
Caenorhabditis elegans
Manganese
Organophosphonates
Toxicity
Oxidative Stress
Antioxidants
Aging of materials
Green Fluorescent Proteins
Hypoglycemic Agents
Oxidants
Theoretical Models

Keywords

  • Caenorhabditis elegans
  • FOXO
  • Free radicals
  • Manganese
  • Organochalcogens
  • Oxidative stress
  • Selenium
  • Tellurium
  • Toxicity

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in Caenorhabditis elegans by preventing oxidative stress. / Avila, Daiana Silva; Benedetto, Alexandre; Au, Catherine; Manarin, Flávia; Erikson, Keith; Soares, Felix Antunes; Rocha, João Batista Teixeira; Aschner, Michael.

In: Free Radical Biology and Medicine, Vol. 52, No. 9, 01.05.2012, p. 1903-1910.

Research output: Contribution to journalArticle

Avila, Daiana Silva ; Benedetto, Alexandre ; Au, Catherine ; Manarin, Flávia ; Erikson, Keith ; Soares, Felix Antunes ; Rocha, João Batista Teixeira ; Aschner, Michael. / Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in Caenorhabditis elegans by preventing oxidative stress. In: Free Radical Biology and Medicine. 2012 ; Vol. 52, No. 9. pp. 1903-1910.
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AU - Manarin, Flávia

AU - Erikson, Keith

AU - Soares, Felix Antunes

AU - Rocha, João Batista Teixeira

AU - Aschner, Michael

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