Detection and inhibition of lipid-derived radicals in low-density lipoprotein.
Detection and inhibition of lipid-derived radicals in low-density lipoprotein.
复制标题
低密度脂蛋白中脂质衍生自由基的检测和抑制。
DOI：
10.1016/j.freeradbiomed.2017.10.388
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Yamada KI.
中科院分区：
文献类型：
--
作者：
Ishida Y;Okamoto Y;Matsuoka Y;Tada A;Janprasit J;Yamato M;Morales NP;Yamada KI.
氧化型低密度脂蛋白（Ox-LDL）与多种氧化性疾病有关。为了阐明所涉及的机制并促进治疗的研究，我们先前开发了一种使用荧光探针2，2，6-三甲基-6-戊基-4-（4-硝基苯并[1，2，5]恶二唑-7-基氨基）哌啶-1-氧基（NBD-Pen）检测脂质衍生自由基的方法。本研究采用NBD-Pen检测铁超载小鼠模型体内和体外氧化低密度脂蛋白（Ox-LDL）中的脂源性自由基。通过使用该方法遵循脂质自由基产生的时间轴，可以用抗氧化剂Trolox成功地治疗铁过载小鼠，导致血浆脂质过氧化、天冬氨酸转氨酶和丙氨酸转氨酶水平的成功降低。此外，使用螯合剂去铁胺（DFX）和Trolox的联合治疗，铁超载小鼠的肝损伤和氧化应激标志物也减少了。与其他现有方法相比，NBD-Pen方法具有高度灵敏度和选择性，适用于靶向最小修饰的LDL。
Oxidized low density lipoprotein (Ox-LDL) is implicated in a variety of oxidative diseases. To clarify the mechanisms involved and facilitate the investigation of therapeutics, we previously developed a detection method for lipid-derived radicals using the fluorescent probe 2,2,6-trimethyl-6-pentyl-4-(4-nitrobenzo[1,2,5]oxadiazol-7-ylamino)piperidine-1-oxyl (NBD-Pen). In this study, NBD-Pen was used to detect lipid-derived radicals in Ox-LDL fromin vitroandin vivosamples using an iron overloaded mouse model. By following the timeline of lipid radical generation using this method, the iron overloaded mice could be successfully treated with the antioxidant Trolox, resulting in successful lowering of the plasma lipid peroxidation, aspartate transaminase and alanine transaminase levels. Furthermore, using a combination therapy of the chelating agent deferoxamine (DFX) and Trolox, liver injury and oxidative stress markers were also reduced in iron overloaded mice. The NBD-Pen method is highly sensitive as well as selective and is suitable for targeting minimally modified LDL compared with other existing methods.