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

View Article: PubMed Central - PubMed

ABSTRACT

Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H2O2 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 H2O2, using phorbol 12-myristate 13-acetate, with and without organochalogens. Released H2O2 was then measured using a chemiluminescent assay over a period of 2 h. The screening identified an organoselenium compound which scavenged H2O2 more effectively than the vitamin E analog, Trolox. We also found that this organoselenium compound protected MC3T3 cells against H2O2-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 H2O2 scavenging and protection suggests that the mechanism of protection is due to the direct scavenging of extracellular H2O2. This compound is a promising modulators of inflammation and could potentially treat diseases involving high levels of oxidative stress.

No MeSH data available.


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(A) Toxicity of different concentration of H2O2 on MC3T3-E1 (B) Effect on MC3T3-E1 protection against H2O2 (pos control) by C1 and Trolox (both at 25 μM), * indicates p < 0.05 compared to positive control. Data expressed as mean ± standard deviation.
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antioxidants-06-00013-f004: (A) Toxicity of different concentration of H2O2 on MC3T3-E1 (B) Effect on MC3T3-E1 protection against H2O2 (pos control) by C1 and Trolox (both at 25 μM), * indicates p < 0.05 compared to positive control. Data expressed as mean ± standard deviation.

Mentions: Antioxidants that do not negatively affect cell viability, may still impair cell differentiation. Thus, we examined the effects of each antioxidant on bone cell viability and differentiation, using MC3T3 pre-osteoblasts. To assess whether C1 can protect MC3T3s against H2O2-induced cell death, we treated the cells with hydrogen peroxide and C1 or Trolox. A dose response study with H2O2 revealed that 300 μM or higher of H2O2 was necessary, in order to induce significant cell toxicity. When cells were treated with toxic levels of H2O2 and slightly higher levels of antioxidant (25 μM, Figure 4), C1, but not Trolox, was able to partially protect MC3T3-E1 against H2O2 (300 μM) mediated toxicity.


Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity
(A) Toxicity of different concentration of H2O2 on MC3T3-E1 (B) Effect on MC3T3-E1 protection against H2O2 (pos control) by C1 and Trolox (both at 25 μM), * indicates p < 0.05 compared to positive control. Data expressed as mean ± standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384176&req=5

antioxidants-06-00013-f004: (A) Toxicity of different concentration of H2O2 on MC3T3-E1 (B) Effect on MC3T3-E1 protection against H2O2 (pos control) by C1 and Trolox (both at 25 μM), * indicates p < 0.05 compared to positive control. Data expressed as mean ± standard deviation.
Mentions: Antioxidants that do not negatively affect cell viability, may still impair cell differentiation. Thus, we examined the effects of each antioxidant on bone cell viability and differentiation, using MC3T3 pre-osteoblasts. To assess whether C1 can protect MC3T3s against H2O2-induced cell death, we treated the cells with hydrogen peroxide and C1 or Trolox. A dose response study with H2O2 revealed that 300 μM or higher of H2O2 was necessary, in order to induce significant cell toxicity. When cells were treated with toxic levels of H2O2 and slightly higher levels of antioxidant (25 μM, Figure 4), C1, but not Trolox, was able to partially protect MC3T3-E1 against H2O2 (300 μM) mediated toxicity.

View Article: PubMed Central - PubMed

ABSTRACT

Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H2O2 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 H2O2, using phorbol 12-myristate 13-acetate, with and without organochalogens. Released H2O2 was then measured using a chemiluminescent assay over a period of 2 h. The screening identified an organoselenium compound which scavenged H2O2 more effectively than the vitamin E analog, Trolox. We also found that this organoselenium compound protected MC3T3 cells against H2O2-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 H2O2 scavenging and protection suggests that the mechanism of protection is due to the direct scavenging of extracellular H2O2. This compound is a promising modulators of inflammation and could potentially treat diseases involving high levels of oxidative stress.

No MeSH data available.


Related in: MedlinePlus