Oh Byeongtaek, Lee Chi H
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, HSB-4242, Kansas City, Missouri, 64108, USA.
Pharm Res. 2014 Sep;31(9):2463-78. doi: 10.1007/s11095-014-1341-3. Epub 2014 Mar 25.
The nanofiber-hydrogel blend containing nitric oxide (NO) donors and reactive oxygen species (ROS) scavengers (Edaravone: EDV) was explored as an advanced strategy for stabilization of Mast cells (MCs) to achieve efficient immune-suppressive effects.
Three types of nanofiber hydrogel composites (Bare-Nanofibers (BNF), Nanofiber-Hydrogels (NF-Gel) and Cross-linked Nanofiber-Hydrogels (NF-Gel-X)), were evaluated. The degranulation rates of MCs were determined by measurement of the extracellular levels of hydrogen peroxide and the released amounts of β-hexosaminidase from the activated-MCs (a-MCs). In addition, the effects of EDV on the selective scavenging of the oxygen radicals and prevention of peroxynitrite formation were evaluated. The roles of a-MCs in re-endothelialization and viability of coronary artery endothelial cells (hPCAECs) were defined using alamar blue and LDH assay, respectively.
Each polymer matrix has unique morphological characteristics. The effects of EDV (~1.0 mM) on the production of NO were greatly influenced by the presence of superoxide or hydroxyl radicals. NF-G-X containing a mixture of EDV and S-Nitroglutathione (GSNO) produced the highest level of NO under the oxidative stress conditions. GSNO alone or a mixture of GSNO and EDV significantly lowered the degranulation rate of a-MCs (GSNO only: 55.8 ± 5.4%; GSNO with EDV: 50.6 ± 0.6%), indicating that NO plays an integral role in degranulation of a-MCs. There were no significant biochemical evidences of cytotoxic effects of GSNO and EDV on the hPCAECs.
Nanofibers containing a mixture of nitric oxide donors and ROS scavengers could be used as a promising strategy to stabilize MCs from the ROS-mediated immune responses.
探索含有一氧化氮（NO）供体和活性氧（ROS）清除剂（依达拉奉：EDV）的纳米纤维-水凝胶混合物，作为稳定肥大细胞（MCs）以实现有效免疫抑制作用的先进策略。
评估了三种类型的纳米纤维水凝胶复合材料（裸纳米纤维（BNF）、纳米纤维-水凝胶（NF-Gel）和交联纳米纤维-水凝胶（NF-Gel-X））。通过测量细胞外过氧化氢水平和活化肥大细胞（a-MCs）释放的β-己糖胺酶量来确定MCs的脱颗粒率。此外，评估了EDV对氧自由基的选择性清除和防止过氧亚硝酸盐形成的作用。分别使用alamar蓝和LDH测定法确定a-MCs在冠状动脉内皮细胞（hPCAECs）再内皮化和活力中的作用。
每种聚合物基质都具有独特的形态特征。超氧化物或羟基自由基的存在极大地影响了EDV（~1.0 mM）对NO产生的影响。含有EDV和S-亚硝基谷胱甘肽（GSNO）混合物的NF-G-X在氧化应激条件下产生的NO水平最高。单独的GSNO或GSNO与EDV的混合物显著降低了a-MCs的脱颗粒率（仅GSNO：55.8±5.4%；GSNO与EDV：50.6±0.6%）,表明NO在a-MCs的脱颗粒中起不可或缺的作用。没有显著的生化证据表明GSNO和EDV对hPCAECs有细胞毒性作用。
含有一氧化氮供体和ROS清除剂混合物的纳米纤维可作为一种有前景的策略，用于稳定MCs免受ROS介导的免疫反应。
