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Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity

Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H(2)O(2) disrupt bone homeostasis, leading to greater bone resorption than bone formation. Organochalcogen compounds could act as free radical trapping agents or glutathione peroxidase mimetics...

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Detalles Bibliográficos
Autores principales: Lu, Xi, Mestres, Gemma, Singh, Vijay Pal, Effati, Pedram, Poon, Jia-Fei, Engman, Lars, Karlsson Ott, Marjam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384176/
https://www.ncbi.nlm.nih.gov/pubmed/28216602
http://dx.doi.org/10.3390/antiox6010013
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author Lu, Xi
Mestres, Gemma
Singh, Vijay Pal
Effati, Pedram
Poon, Jia-Fei
Engman, Lars
Karlsson Ott, Marjam
author_facet Lu, Xi
Mestres, Gemma
Singh, Vijay Pal
Effati, Pedram
Poon, Jia-Fei
Engman, Lars
Karlsson Ott, Marjam
author_sort Lu, Xi
collection PubMed
description Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H(2)O(2) disrupt bone homeostasis, leading to greater bone resorption than bone formation. Organochalcogen compounds could act as free radical trapping agents or glutathione peroxidase mimetics, reducing oxidative stress in inflammatory diseases. In this report, we synthesized and screened a library of organoselenium and organotellurium compounds for hydrogen peroxide scavenging activity, using macrophagic cell lines RAW264.7 and THP-1, as well as human mono- and poly-nuclear cells. These cells were stimulated to release H(2)O(2), using phorbol 12-myristate 13-acetate, with and without organochalogens. Released H(2)O(2) was then measured using a chemiluminescent assay over a period of 2 h. The screening identified an organoselenium compound which scavenged H(2)O(2) more effectively than the vitamin E analog, Trolox. We also found that this organoselenium compound protected MC3T3 cells against H(2)O(2)-induced toxicity, whereas Trolox did not. The organoselenium compound exhibited no cytotoxicity to the cells and had no deleterious effects on cell proliferation, viability, or alkaline phosphatase activity. The rapidity of H(2)O(2) scavenging and protection suggests that the mechanism of protection is due to the direct scavenging of extracellular H(2)O(2). This compound is a promising modulators of inflammation and could potentially treat diseases involving high levels of oxidative stress.
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spelling pubmed-53841762017-04-10 Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity Lu, Xi Mestres, Gemma Singh, Vijay Pal Effati, Pedram Poon, Jia-Fei Engman, Lars Karlsson Ott, Marjam Antioxidants (Basel) Article Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H(2)O(2) disrupt bone homeostasis, leading to greater bone resorption than bone formation. Organochalcogen compounds could act as free radical trapping agents or glutathione peroxidase mimetics, reducing oxidative stress in inflammatory diseases. In this report, we synthesized and screened a library of organoselenium and organotellurium compounds for hydrogen peroxide scavenging activity, using macrophagic cell lines RAW264.7 and THP-1, as well as human mono- and poly-nuclear cells. These cells were stimulated to release H(2)O(2), using phorbol 12-myristate 13-acetate, with and without organochalogens. Released H(2)O(2) was then measured using a chemiluminescent assay over a period of 2 h. The screening identified an organoselenium compound which scavenged H(2)O(2) more effectively than the vitamin E analog, Trolox. We also found that this organoselenium compound protected MC3T3 cells against H(2)O(2)-induced toxicity, whereas Trolox did not. The organoselenium compound exhibited no cytotoxicity to the cells and had no deleterious effects on cell proliferation, viability, or alkaline phosphatase activity. The rapidity of H(2)O(2) scavenging and protection suggests that the mechanism of protection is due to the direct scavenging of extracellular H(2)O(2). This compound is a promising modulators of inflammation and could potentially treat diseases involving high levels of oxidative stress. MDPI 2017-02-14 /pmc/articles/PMC5384176/ /pubmed/28216602 http://dx.doi.org/10.3390/antiox6010013 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lu, Xi
Mestres, Gemma
Singh, Vijay Pal
Effati, Pedram
Poon, Jia-Fei
Engman, Lars
Karlsson Ott, Marjam
Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity
title Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity
title_full Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity
title_fullStr Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity
title_full_unstemmed Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity
title_short Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity
title_sort selenium- and tellurium-based antioxidants for modulating inflammation and effects on osteoblastic activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384176/
https://www.ncbi.nlm.nih.gov/pubmed/28216602
http://dx.doi.org/10.3390/antiox6010013
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