Lu Xi, Mestres Gemma, Singh Vijay Pal, Effati Pedram, Poon Jia-Fei, Engman Lars, Ott Marjam Karlsson
Department of Engineering Science, Applied Materials Science, Uppsala University, Box 534, Uppsala 751 21, Sweden.
Department of Engineering, Microsystems Technology, Uppsala University, Box 534, Uppsala 751 21, Sweden.
Antioxidants (Basel). 2017 Feb 14;6(1):13. doi: 10.3390/antiox6010013.
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.
氧化应激增加在骨疾病的病因学中起重要作用。过氧化氢水平升高会破坏骨稳态，导致骨吸收大于骨形成。有机硫属元素化合物可作为自由基捕获剂或谷胱甘肽过氧化物酶模拟物，减轻炎症性疾病中的氧化应激。在本报告中，我们合成并筛选了一系列有机硒和有机碲化合物，以巨噬细胞系RAW264.7和THP-1以及人单核和多核细胞为模型，检测其清除过氧化氢的活性。使用佛波酯12-肉豆蔻酸酯13-乙酸酯刺激这些细胞释放过氧化氢，同时添加或不添加有机硫属元素化合物。然后在2小时内使用化学发光法测定释放的过氧化氢。筛选出一种有机硒化合物，其清除过氧化氢的效果比维生素E类似物Trolox更有效。我们还发现这种有机硒化合物可保护MC3T3细胞免受过氧化氢诱导的毒性，而Trolox则不能。该有机硒化合物对细胞无细胞毒性，对细胞增殖、活力或碱性磷酸酶活性无有害影响。过氧化氢清除和保护的快速性表明，保护机制是由于直接清除细胞外过氧化氢。这种化合物是一种有前景的炎症调节剂，可能治疗涉及高水平氧化应激的疾病。
