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

Biomedical and Life Sciences

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Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in Caenorhabditis elegans by preventing oxidative stress. / Avila, Daiana Silva; Benedetto, Alexandre; Au, Catherine et al.
In: Free Radical Biology and Medicine, Vol. 52, No. 9, 01.05.2012, p. 1903-1910.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Avila, DS, Benedetto, A, Au, C, Manarin, F, Erikson, K, Soares, FA, Rocha, JBT & Aschner, M 2012, 'Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in Caenorhabditis elegans by preventing oxidative stress', Free Radical Biology and Medicine, vol. 52, no. 9, pp. 1903-1910. https://doi.org/10.1016/j.freeradbiomed.2012.02.044

APA

Avila, D. S., Benedetto, A., Au, C., Manarin, F., Erikson, K., Soares, F. A., Rocha, J. B. T., & Aschner, M. (2012). Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in Caenorhabditis elegans by preventing oxidative stress. Free Radical Biology and Medicine, 52(9), 1903-1910. https://doi.org/10.1016/j.freeradbiomed.2012.02.044

Vancouver

Avila DS, Benedetto A, Au C, Manarin F, Erikson K, Soares FA et al. Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in Caenorhabditis elegans by preventing oxidative stress. Free Radical Biology and Medicine. 2012 May 1;52(9):1903-1910. Epub 2012 Mar 8. doi: 10.1016/j.freeradbiomed.2012.02.044

Author

Avila, Daiana Silva ; Benedetto, Alexandre ; Au, Catherine et al. / 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.

Bibtex

@article{ef08daf6bcf04a0997c04d79112a550f,

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

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.",

keywords = "Animals, Caenorhabditis elegans, Lethal Dose 50, Manganese, Microscopy, Fluorescence, Organoselenium Compounds, Oxidative Stress, Reactive Oxygen Species, Tellurium, Journal Article, Research Support, N.I.H., Extramural",

author = "Avila, {Daiana Silva} and Alexandre Benedetto and Catherine Au and Fl{\'a}via Manarin and Keith Erikson and Soares, {Felix Antunes} and Rocha, {Jo{\~a}o Batista Teixeira} and Michael Aschner",

year = "2012",

month = may,

day = "1",

doi = "10.1016/j.freeradbiomed.2012.02.044",

language = "English",

volume = "52",

pages = "1903--1910",

journal = "Free Radical Biology and Medicine",

issn = "0891-5849",

publisher = "ELSEVIER SCIENCE INC",

number = "9",

}

RIS

TY - JOUR

T1 - Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in Caenorhabditis elegans by preventing oxidative stress

AU - Avila, Daiana Silva

AU - Benedetto, Alexandre

AU - Au, Catherine

AU - Manarin, Flávia

AU - Erikson, Keith

AU - Soares, Felix Antunes

AU - Rocha, João Batista Teixeira

AU - Aschner, Michael

PY - 2012/5/1

Y1 - 2012/5/1

N2 - 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.

AB - 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.

KW - Animals

KW - Caenorhabditis elegans

KW - Lethal Dose 50

KW - Manganese

KW - Microscopy, Fluorescence

KW - Organoselenium Compounds

KW - Oxidative Stress

KW - Reactive Oxygen Species

KW - Tellurium

KW - Journal Article

KW - Research Support, N.I.H., Extramural

U2 - 10.1016/j.freeradbiomed.2012.02.044

DO - 10.1016/j.freeradbiomed.2012.02.044

M3 - Journal article

C2 - 22406322

VL - 52

SP - 1903

EP - 1910

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 9

ER -

Research

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